Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and radiographic screening for the current study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Patients with known central nervous system (CNS) involvement may be excluded; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damage
Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar puncture\r\n* Note: lumbar puncture can be performed at the time of diagnosis and does not need to be repeated unless there is a change in neurological status or it was performed more than 14 days prior to study entry
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, with the following exceptions: \r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of clinical stability upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to randomization\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Children who have histologically proven diagnoses of the following types of CNS tumor are eligible for entry onto this protocol; the exclusive focus is on medulloblastoma and other CNS primitive neuro-ectodermal tumors (PNET) of the brain or spinal cord
All children less than 120 months (10years) of age, irrespective of clinical stage, with a diagnosis of any of the following CNS PNET are eligible: pineoblastoma, all primary CNS-PNET, including CNS/cerebral neuroblastoma, CNS/cerebral ganglioneuroblastoma, medulloepithelioma, ependymoblastoma, embryonal tumor with abundant neuropil and true rosettes (ETANTR; more recently designated as \embryonal tumor with multilayered rosettes\ or \ETMR\), melanotic medulloblastoma and/or medullomyoblastoma, CNS supratentorial PNET, spinal cord PNET, brainstem PNET are all eligible, regardless of patterns of (divergent) differentiation
All diagnoses other than medulloblastoma and CNS PNET - these include: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord.; All choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
Patients with CNS tumors or known CNS metastases will be excluded from this trial; patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows not evidence for active disease; patients with extra axial disease (e.g. skull [bone] metastasis that do not invade the dura) may enroll if there is no evidence for CNS edema associated with the lesion
Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed
Patients with known symptomatic, untreated central nervous system (including brain, spinal cord)\r\n* Patients who have a history of brain/central nervous system (CNS) metastasis are eligible for the study provided that all the following criteria are met:\r\n** Brain/CNS metastases which have been treated\r\n** No evidence of disease progression for >= 3 months before the first dose of study drug \r\n** No hemorrhage after treatment\r\n** Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228\r\n** No ongoing requirement for dexamethasone or anti-epileptic drugs
Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent); patients with untreated CNS metastases are eligible if they are not symptomatic and the lesions are less than 1 cm in size
Patients with central nervous system (CNS) metastases must have all lesions adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression; patients must not have required steroids for at least 14 days prior to registration
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia; Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis, or other significant CNS abnormalities
Patients with central nervous system (CNS) metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.\r\n** No neurosurgical resection or brain biopsy within 28 days prior to randomization\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to randomization \r\n** Screening CNS radiographic study >= 28 days from completion of radiotherapy and >= 14 days from discontinuation of corticosteroids
Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis, active ALL in the CNS confirmed by cerebrospinal fluid (CSF) analysis, or other significant CNS abnormalities
Patients must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration; patients with CNS3 are excluded from the trial; patients with CNS1 or CNS2 will be eligible, but will be monitored for CNS involvement; note that intrathecal methotrexate administered during the pre-study lumbar puncture may count as the first dose of intrathecal therapy required as part of the study
Patients with known or suspected central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded; however, subjects with controlled brain metastases will be allowed to enroll; controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator’s judgment is sufficient)
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to treatment start\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Patients with central nervous system (CNS) metastases with the following exceptions: Patient untreated CNS metastases with 5 or fewer sites of disease, with no single site larger than 20 mm, are eligible if they are asymptomatic and not requiring steroids at any dose; patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays; patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
Participants with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:\r\n* Disease outside the CNS is present\r\n* No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* Not requiring anti-convulsants for symptomatic control\r\n* Minimum of 3 weeks between completion of CNS radiotherapy and cycle 1 day 1 and recovery from significant (grade >= 3) acute toxicity with no ongoing requirement for corticosteroid
Patients with known active CNS leukemia.
Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
Subject has current central nervous system (CNS) or leptomeningeal metastases or history of CNS or leptomeningeal metastases.
Active, untreated central nervous system (CNS) metastasis (subjects with brain metastases who are identified at screening may be rescreened after the lesion[s] have been appropriately treated and subjects are off corticosteroids)
Patients must not have active central nervous system (CNS) involvement (by clinical evaluation); patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration; note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not required
Participants with evidence for central nervous system (CNS) lymphoma on neurological exam and/or with radiographic evidence (if radiographic studies are done) of CNS lymphoma (inclusive of parenchymal, vitreal, or leptomeningeal involvement)
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug; screening with CNS imaging studies (CT or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days; previously treated CNS disease with documented cleared CSF will be allowed
ELIGIBILITY CRITERIA - PHASE II (ARM D): Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days; previously treated CNS disease with documented cleared CSF will be allowed
Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollment
Participants with primary CNS malignancies or tumors with CNS metastases as the only site of disease, will be excluded
Participants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll)
Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: disease outside the CNS is present; no clinical evidence of progression since completion of CNS-directed therapy; minimum of 2 weeks between completion of radiotherapy and cycle 1 day 1 and recovery from significant (grade ? 3) acute toxicity with no ongoing requirement for > 10 mg of prednisone per day or an equivalent dose of other corticosteroid; NOTE: patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment
Untreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS disease
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for ? 6 months prior to randomization; Note: Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Participants with known brain metastases may be enrolled in this study if radiation therapy and/or surgery have been completed with a minimum of 4 weeks of stable disease demonstrated on evaluation by magnetic resonance imaging (MRI); such participants must no longer require treatment with corticosteroids or enzyme inducing anti-epileptic medications for their central nervous system (CNS) disease
Has CNS metastases or symptomatic CNS involvement
Known CNS disease including, but not limited to, metastases
Clinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone > 10 mg daily within 2 weeks prior to study entry for CNS symptoms
Known active CNS metastases or carcinomatous meningitis.
Central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* >= 28 days from prior therapy completion (including radiation and/or surgery) to registration\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma
Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment
Subjects with symptomatic CNS metastases who are neurologically unstable and/or require an increased dose of steroid to manage CNS symptoms within 1 week prior to the first day of treatment are excluded\r\n* Subjects with brain or leptomeningeal metastases that do not meet the above criteria are allowed\r\n* Symptomatic disease is allowed as long as symptoms are controlled and stable
Have known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days.
Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
Primary central nervous system (CNS) malignancy or CNS metastases.
Prior central nervous system (CNS) disease is allowed if stable for at least one month since whole brain radiation therapy, and 2 weeks since stereotactic radiotherapy, and not requiring steroids; patients whose CNS disease was surgically treated may be enrolled if stable for at least one month, and not requiring steroids
Patients with asymptomatic CNS involvement are allowed.
Symptomatic CNS involvement.
Known CNS metastases
CNS metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to randomization.
Active, non-stable brain metastases or CNS disease
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.
Participants must have progressive CNS lesions, as defined by one of the following:\r\n* Patients may have multiple progressive CNS lesions, some of which have been treated by stereotactic radiosurgery (SRS) or surgery; patients are eligible if they have one or more untreated (by surgery or SRS) progressive lesions that is measurable\r\n* Patients have measurable residual or progressive lesions after surgery\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis); biopsy can be considered for definitive diagnosis\r\n* Patients who have previously been treated with systemic therapy for CNS metastases are eligible
Acute symptomatic CNS hemorrhage
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** There are no more than 3 lesions, =< 1 cm in size each\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
COHORT 1: Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapy
COHORT 2: Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapy
Patients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least 2 weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of < 10 mg daily prednisone or equivalent
Symptomatic central nervous system (CNS) metastasis(es). Note: Baseline CT/MRI of the brain is required for SCLC patients enrolled in Arm 4. Patients with previously treated CNS metastasis(es) are eligible if the patients with previously treated CNS metastasis(es) are asymptomatic and radiographically/clinically stable and not requiring steroids within 4 weeks prior to first dose. Note: Non-SCLC patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) scan of the brain unless it is considered standard of care.
Known CNS disease including, but not limited to, metastases
Participants with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days prior to screening
Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases\r\n* Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement
Clinical Evidence of CNS disease
Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 4 weeks and must be off steroid treatment for 2 weeks prior to study enrollment
Symptomatic central nervous system (CNS) involvement or lymphangitic metastasis. Stable or improving CNS disease that is not under active treatment after receipt of adequate therapy is allowed.
Leptomeningeal disease as the only site of CNS involvement
CNS metastases if not previously treated and stable for at least 2 months per imaging and clinical assessment.
Have central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ?14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.
Patients with central nervous system involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice; for patients with central nervous system (CNS) disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the Memorial Sloan-Kettering (MSK) principal investigator (PI); once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days
Patients with primary CNS tumors or symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable;
History of central nervous system (CNS) disease is acceptable if effectively treated and demonstrated stable disease for >= 2 months from protocol tissue procurement
Previously untreated CNS metastases or progressive CNS metastases
Patients who have known brain metastasis; patients whose central nervous system (CNS) metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable are eligible
Subjects with central nervous system metastasis; with the exception of subjects who have stable brain metastases as defined as off steroids and no CNS progress for 6 months after CNS treatment.
Participants with known or suspected uncontrolled CNS metastases or with the CNS as the only site of active disease
Have metastasis to the CNS that is symptomatic and/or requires therapy with corticosteroids or anti-convulsant medication. However, subjects who have completed treatment (radiation therapy) for CNS metastases and do not require continued treatment with corticosteroids or anti-convulsants may be enrolled in this study.
Participants with known untreated brain metastases should be excluded from this clinical trial; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to study entry; subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first study treatment
Subjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable.
Has known active CNS metastases and/or carcinomatous meningitis
Symptomatic and/or untreated CNS metastases
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable and/or require radiation therapy are excluded;\r\n* Participants with brain metastases that do not meet the above criteria in the opinion of the treating investigator \r\n* Symptomatic disease is allowed as long as symptoms are controlled and stable
History of unstable central nervous system (CNS) metastases or seizure disorder related to the malignancy; however, those subjects who were treated for prior CNS metastases and who are asymptomatic may participate in the study as long as they are not receiving treatment with steroids.
CNS status \r\n* Subjects with ALL\r\n** Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n*** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs)\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with lymphoma\r\n** Subjects must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have previously been treated for CNS disease and who have the following CNS status will be eligible:\r\n*** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm
Subjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of >= 5/uL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia)
CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity
Participants with Central Nervous System (CNS) metastases are not eligible, unless they have completed local therapy for at least 4 weeks and have discontinued the use of corticosteroids for this indication or are on a tapering regimen of corticosteroids (defined as ?10 milligrams [mg] prednisolone equivalent) before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
Participants with known central nervous system (CNS) leukemia involvement should be excluded from this clinical trial; patients with a history of CNS leukemia that has been treated and is no longer active as judged by the treating investigator are eligible
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded
EXCLUSION - TREATMENT: Central nervous system (CNS) abnormalities: presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of cerebrospinal fluid (CSF) with ? 5 white blood cells (WBCs) per mm^3; history or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
Patients with treated central nervous system (CNS) metastases will be eligible if not symptomatic, the CNS disease has been stable for a minimum of 6 weeks and the patient requires less than or equal to the equivalent of 2 mg/day of dexamethasone
Patients with known symptomatic CNS metastases or lepotomeningeal disease requiring steroids.
Central Nervous System (CNS) Function defined as subjects with a known history of seizures must have well-controlled seizures and may not be receiving enzyme-inducing anti-convulsants, CNS toxicity <= Grade 2.
Patients with known involvement of the CNS by malignancy will be excluded.
Patients with known leptomeningeal or brain metastases should be excluded from this clinical trial; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
Malignant CNS disease that has not been definitively treated
Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
Subject has symptomatic CNS metastases.
Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study treatment.
Evidence of CNS involvement by NHL
Untreated or actively progressing CNS lesions (carcinomatous meningitis)
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and subjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS involvement with their lymphoma must have completed effective treatment of their CNS disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imaging
Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS disease may participate provided they are stable (without evidence of active disease by imaging for at least 4 weeks prior to the first dose of treatment, and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to D1 of treatment
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
History of seizures, central nervous system tumors or CNS metastasis. Due to the incidence of silent CNS metastases in patients with advanced NSCLC, such patients must undergo mandatory screening with brain MRI or CT scan to determine eligibility.
If patient has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: Patient has measurable disease outside CNS; Patient does not have metastases to midbrain, pons, medulla or spinal cord; Patient is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); Patient has not had whole-brain radiation within 6 weeks prior to study enrollment; Patient has stable CNS disease as demonstrated by at least 4 weeks of stability between the last intervention scan and the study screening scan
Subjects with a history of or active CNS tumors or metastases from non-CNS tumors.
The patient has known active or suspected brain or leptomeningeal metastases. (Central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 3 months following radiation therapy or other locoregional ablative therapy to the CNS.
Radiographic evidence of CNS metastases
Subjects with CNS lesions are excluded
Patients with uncontrolled central nervous system (CNS) metastatic involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:\r\n* > 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapy\r\n* Not receiving anti-convulsive medications that were started for brain metastases
CNS metastases, unless treated w/ surgery, whole brain radiation or stereotactic radiosurgery, and stable disease ?8 wks w/o steroid use for ?4 wks prior to study drug
Active CNS involvement by malignant cells (? 2 months from the conditioning)
Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments; participants with a history of treated asymptomatic CNS metastases are eligible
Subjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or isolated CNS disease which are eligible for definitive CNS directed radiation therapy will be excluded
Patients with known brain metastases should be excluded from this clinical trial; patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS recurrence-free for the 1-year period
Patients with known leptomeningeal or brain metastases; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring > 5 mg/day of dexamethasone (or equivalent) to control CNS disease; note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed > 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
Symptomatic or untreated Central nervous system (CNS) disease, Subjects with a history of CNS disease (leukemia, lymphoma or myeloma) are permitted to enrol if they have previously received appropriate therapy and CNS remission has been documented. Subject with primary CNS lymphoma (defined as isolated CNS lymphoma without systemic involvement) are excluded from study.
Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
Patients with active central nervous system (CNS) metastases or leptomeningeal involvement by tumor (patients with a history of brain metastases who have successfully treated for brain metastasis by surgery or radiation and who have not had any evidence of the new or progressive CNS disease for more than 12 months are eligible)
If they have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trial
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease, are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
TREATMENT WITH SJCAR19: CNS-1/CNS-2 disease with neurologic changes
Subjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.
Active central nervous system (CNS) disease\r\n* Definition: any patient receiving active CNS therapy (defined as more than 1 intrathecal treatment per week or current radiation therapy to brain); if patient has a history of CNS disease: must have cerebrospinal fluid (CSF) sampling within 28 days of enrollment that is negative for leukemia; intrathecal chemotherapy for patients without active CNS disease is allowed (e.g., ongoing primary or secondary prophylaxis for patients who cleared the CSF prior to study enrollment); CSF sample is not required for enrollment for patients with no history of CNS disease
Adequate central nervous system (CNS) function defined as:\r\n* Patients with seizure disorder may be enrolled if on allowed anti-convulsants and well controlled; benzodiazepines and gabapentin are acceptable\r\n* CNS toxicity < grade 2
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Central nervous system (CNS) status\r\n* Subjects with leukemia with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs)\r\n** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n*** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts\r\n*** CNS 2b: ? 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts\r\n*** CNS 2c: ? 10/uL RBCs; ? 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with lymphoma\r\n** Subjects must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have been previously treated for CNS disease but have no evidence of disease at screening are eligible
Subjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ? 5/uL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia and/or radiographic signs of leptomeningeal disease)
Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)
Active (i.e., symptomatic or progressing) CNS metastases. Subjects with CNS metastases are eligible for the trial if:
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
STRATUM B: Participants with recurrent, progressive, or refractory CNS tumors as confirmed through central pathology review
Known active brain or central nervous system metastasis (less than 2 months out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (< 3 months) or clinically significant cerebrovascular accident (< 3 months); in order to be eligible patients must have repeat central nervous system (CNS) imaging at least two months after definitive treatment showing stable CNS disease; patients with evidence of intratumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade =< 1 and has been shown to be stable on two consecutive imaging scans
Patients with active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions); however, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for >= 3 weeks
History or clinical signs of meningeal or active CNS involvement
Subjects with symptomatic untreated CNS metastases are excluded\r\n* Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment\r\n* In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment
No progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastases
Oral hydroxyurea and/or one dose of cytarabine (up to 2 g/m^2) for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment through cycle 1, as needed, for clinical benefit and after discussion with the principal investigator (PI); concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
Participants with primary central nervous system (CNS) tumors, or with CNS metastases as the only site of active disease (Participants with controlled brain metastases; however, will be allowed to enroll)
Uncontrolled central nervous system (CNS) metastasis; patients with CNS metastasis can be eligible if definitively treated with radiotherapy or surgery
GENERAL: Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases.
Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted. Patients with a known history of CNS disease or leukemic brain metastasis must have been treated locally, have at least 3 consecutive lumbar punctures (LPs) with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable).
Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of Study Drug, off or on a stable dose of corticosteroids. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy. (Applicable to tumor types of non-CNS primary origin only)
Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is required only if there is a clinical suspicion of CNS involvement by leukemia during screening.
CNS abnormalities
Presence of CNS-3 disease or CNS-2 disease with neurological changes
Patients with treated or untreated asymptomatic CNS metastases may be allowed to enroll.
Patients with primary CNS tumors are ineligible.
Central nervous system (CNS) metastases, unless previously treated by either radiation therapy and/or surgical resection, clinically stable for at least 60 days and off corticosteroids; patients with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered\r\n(surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the patient is clinically stable; the patient is off corticosteroids
Known central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 30 days prior to the start of study drug
Concurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed
Patients with central nervous system (CNS) progression (parenchymal but not leptomeningeal) are eligible if CNS metastases are treated and deemed stable (with a repeat computed tomography [CT]/magnetic resonance imaging [MRI] imaging study) prior to the enrollment date; if radiation is used to treat CNS parenchymal disease, a 2 week washout period will apply
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases.\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS.\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm).\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage.\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.\r\n** No neurosurgical resection or brain biopsy within 28 days prior to start of study treatment.\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to start of study treatment.\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids.
Participants must not have suspected, known, or progressive CNS metastases, have untreated CNS metastases, or have the CNS as the only site of disease
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and\r\nsubjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a dose of less than 10 mg per day
Active central nervous system (CNS) metastasis; NOTE: Patients with prior brain metastases that are asymptomatic without corticosteroid use and stable or improved >= 90 days after treatment with surgery or radiation are not excluded
Dose Escalation Cohorts: Active CNS disease, including history of CNS metastases.
MTD/MFD Expansion Cohorts: CNS disease, including history of CNS metastases, that was not stable during the last 6 months.
Has known active CNS metastases and/or carcinomatous meningitis.
Any history of CNS metastases that is not adequately treated (surgery or radiation) > 14 days prior to registration
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Untreated CNS or leptomeningeal metastasis\r\n* Note: CNS or leptomeningeal disease must be stable for >= 3 months prior to registration
History of primary CNS malignancy, or leptomeningeal disease or CNS metastases
Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria:\r\n* Presence of measurable disease outside the CNS\r\n* No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed)\r\n* Absence of leptomeningeal disease
Has known active central nervous system (CNS) disease and/or lymphomatous involvement; subjects with previously treated CNS lymphoma and/or lymphomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
Known active central nervous system metastases and/or lymphomatous meningitis; patients with isolated cerebrospinal fluid (CSF) involvement detectable by flow cytometry are eligible if clinically asymptomatic and if abnormal B cells are reported to be less than 3% by flow cytometry; subjects with previously treated central nervous system (CNS) disease may participate provided: 1) any CNS-directed treatment was completed at least 1 month prior to enrollment, 2) imaging studies and CSF evaluation show no evidence of disease progression, and 3) any neurologic symptoms have returned to baseline
Patients requiring radiation for CNS diseases are excluded (CNS defined as brain soft tissue/intra parenchymal metastases within the gray and white matter of the brain and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal carcinomatous disease)
History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis. Patients with active CNS leukemia will be excluded.
Subjects with active central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks.
Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)
CNS involvement with disease refractory to intrathecal chemotherapy
Uncontrolled metastases to the central nervous system (CNS) or cytological/radiographic evidence of leptomeningeal carcinomatosis. Participants with brain metastases (other than leptomeningeal carcinomatosis) are eligible provided they do not require ongoing steroids and have shown clinical and radiographic stability for at least 28 days after definitive therapy. Primary glioblastoma is allowed.
CNS status \r\n* Subjects with ALL\r\n** Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n*** CNS 1, defined as absence of blasts in CSF on cytospin preparation, regardless of the number of white blood cells (WBCs);\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with DLBCL\r\n** Subjects must have no signs or symptoms of CNS disease or no detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have been previously treated for CNS disease but have no evidence of disease at screening are eligible
CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity
Subjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the subject is: > 4 weeks from prior therapy completion (including radiation and/or surgery); clinically stable with respect to the CNS tumor at the time of study entry; not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; not receiving anti-convulsive medications (that were started for brain metastases).
Known or suspected central nervous system (CNS) metastases, unless at least one month has passed since last local CNS therapy and there is no evidence for recurrent or progressive CNS disease on follow up imaging; participants may remain on steroids for CNS disease if they are taking a stable dose
Patients with untreated, controlled asymptomatic central nervous system (CNS) lesions are allowed in this trial as long as the CNS is not a site of progressive disease on alectinib monotherapy; if the CNS is a site of progressive disease on alectinib monotherapy, treatment of CNS lesions is required for enrollment
Participants who experienced progression of CNS lesions on alectinib who have not received local CNS therapies (radiation, surgery) to address the lesions; CNS imaging obtained at least 21 days after completion of radiation is required for confirmation of response
Any approved anticancer therapy for treatment purpose is not allowed, or need to be stopped at least 2 weeks prior to initiation of study treatment; however, the following are allowed: a. endocrine therapy (selective estrogen receptor modulator [SERM], aromatase inhibitor, fulvestrant) b. palliative radiotherapy for bone metastases > 1 week prior to study treatment c. stable brain metastasis and asymptomatic treated central nervous system (CNS) metastases are allowed, patient must show stable disease by CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
have known uncontrolled or symptomatic CNS metastases;
History or evidence of central nervous system (CNS) metastases (patients with pretreated metastases are eligible under certain conditions)
Symptomatic brain or central nervous system (CNS) metastases; previously treated and stable CNS disease is allowed
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least 6 weeks prior to study registration in the opinion of the investigator and does not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: Only patients with a known history or indication of CNS disease are required to have CNS imaging prior to study entry
Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments; subjects with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:\r\n* Evaluable or measurable disease outside the CNS\r\n* No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n* No history of intracranial or spinal cord hemorrhage\r\n* No evidence of significant vasogenic edema\r\n* o ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose allowed\r\n* No stereotactic radiation, whole-brain radiation within 4 weeks prior to cycle 1 day 1\r\n* Subjects with CNS metastases treated by neurosurgical resection or brain biopsy within 3 months prior to cycle 1 day 1 will be excluded\r\n* Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study\r\n* Screening CNS radiographic study >= 4 weeks since completion of radiotherapy or surgical resection and >= 2 weeks since discontinuation of corticosteroids
Subject has symptomatic CNS metastases.
Known central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that have been effectively treated to complete remission (< 5 white blood cell [WBC]/mm^3 and no blasts in cerebrospinal fluid [CSF]) will be eligible.
Patients with a history of central nervous system (CNS) involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for cyclophosphamide (Cy)/TBI arm; patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment
History or presence of clinically relevant disorder affecting the central nervous system (CNS) such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis, with the exception of a history of CNS lymphoma that is controlled with intrathecal therapy.
Known active DLBCL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis).
Subjects with CNS metastases are only eligible if the CNS metastases are treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment); in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Active central nervous system (CNS) disorder or seizure disorder or known CNS disease or neurologic symptomatology
Active CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be off steroids.
Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: \r\n* Are asymptomatic, and \r\n* Have no requirement for steroids or enzyme-inducing anti-convulsants in the prior 28 days
Carcinomatous meningitis, untreated central nervous system (CNS) disease or symptomatic CNS metastasis. Patients with previously treated CNS metastasis (excluding carcinomatous meningitis) may participate if they are stable (without evidence of progression by imaging, using identical imaging modality at each assessment, for at least 4 weeks prior to first dose of study treatment), have no evidence of new or emerging CNS metastasis, and are not using steroids for at least 7 days prior to first dose of study treatment
Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
Treated central nervous system (CNS) metastasis allowed if treatment is completed >= 8 weeks prior to enrollment; patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after completion of radiation therapy; CNS disease must be stable or regressed on repeat imaging performed at least 4 weeks after completion of therapy
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Patients with known history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registration and do not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: CNS imaging is only required at baseline for patients with known history of CNS metastases
Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within 4 weeks of registration or progressive neurological decline\r\n* Patients with primary CNS lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment; similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS disease
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy =< 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation =< 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\nNo neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in the central nervous system (CNS) unless the patient\r\n* Is > 6 months from definitive therapy,\r\n* Has a negative imaging study within 4 weeks before study entry (informed consent form [ICF] signature for full study) and\r\n* Is clinically stable with respect to the tumor at the time of study entry
Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
Active central nervous system (CNS) disease; history of CNS metastases or cord compression is allowable if the patient has been clinically stable for at least 4 weeks since completion of definitive treatment and is off systemic steroids; in the case of brain metastases, the patient must have stable or improved imaging at least 4 weeks after completion of definitive treatment; if there is evidence of active leptomeningeal disease, the patient is ineligible
Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
Active CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology; in case of AML active CNS involvement as detected by lumbar puncture or neuro-imaging (only to be done if clinically indicated)
CELL PROCUREMENT: Lumbar puncture must be performed prior to procurement and subjects with evidence of CNS3 disease will be excluded from study entry; subjects with concurrent CNS3 disease and bone marrow relapse who have responded to CNS-directed therapy prior to enrollment/lymphodepletion will be allowed to participate; subjects with CNS2 disease and concurrent bone marrow relapse will be eligible; intrathecal chemotherapy will be allowed to continue between lymphodepleting chemotherapy and cell infusion
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** Screening CNS radiographic study ? 4 weeks from completion of radiotherapy and ? 2 weeks from discontinuation of corticosteroids
Central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Current untreated brain metastasi(e)s; if treated history of central nervous system (CNS) metastases, should have completed radiation or surgery at least 12 weeks prior and off systemic corticosteroids
Patients with known central nervous system (CNS) involvement may be excluded; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damage
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and avelumab will be at least 14 days OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is longer; the toxicity from prior therapy should have resolved to grade =< 1, however alopecia and sensory neuropathy grade =< 2 is acceptable; the half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochures, or drug-administration manuals) and will be documented in the protocol eligibility document; use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and will not require a washout; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted; patients with CNS disease or leukemic brain metastasis must have been treated locally and be clinically stable for at least 2 weeks prior to enrollment and have no ongoing neurological symptoms that are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable)
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review/CIV
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review
Patients are excluded if they have active CNS metastases. Patients with history of CNS metastases must have MRI scans that show stability of brain metastases for 8 weeks.
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by principal investigator (PI) and radiology review
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least 6 weeks prior to study registration in the opinion of the investigator and do not require corticosteroids (of any dose) for symptomatic management; NOTE: Patients are not required to have CNS imaging prior to study entry
Subjects with history of central nervous system (CNS) disease are allowed if at the time of day 1 of the study there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to the first study drug administration in a subject with no clinical signs of CNS disease
Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment surgery, radiation, or both
Uncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are radiographically unstable, symptomatic and/or requiring escalating doses of corticosteroids)
Patients with history of central nervous system (CNS) lymphoma can be enrolled if the CNS disease has been controlled with therapy for a minimum of 4 weeks; brain magnetic resonance imaging (MRI) is not required for eligibility
Subjects with untreated symptomatic central nervous system (CNS) metastases are excluded\r\n* Subjects are eligible if symptomatic CNS metastases are treated and subjects have neurologically returned to baseline (except for residual signs and symptoms related to CNS treatment) for at least 7 days prior to first dose of study treatment\r\n** Subjects must be off corticosteroids for at least 7 days prior to first dose of study treatment
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously resected brain metastases may participate provided it has been at least 6 months and no CNS progression has been identified
Patients with untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease) are excluded\r\n* Note: Subjects with previously treated CNS metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management are permitted to enroll
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
If prior central nervous system (CNS) leukemia, it must be treated and in CNS CR
Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
mCRPC EXPANSION COHORT: Patients with evidence of CNS metastasis or leptomeningeal disease within 1 year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
Has known active central nervous system (CNS) leukemia and/or leukemic meningitis; subjects with previously treated CNS leukemia may participate provided they are stable (e.g., without evidence of active disease by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) and have no evidence of leukemic blasts on analysis of cerebrospinal fluid (CSF)
Concurrent systemic high-dose corticosteroids when used intermittently in an antiemetic regimen, for central nervous system (CNS) metastases management, or as a part of the premedication regimen are allowed
Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
Patients with untreated central nervous system (CNS) metastases; patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiotherapy, focal radiotherapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization; the patient may have no evidence of grade >= 1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before randomization)
Patients diagnosed with primary central nervous system (CNS) or with CNS metastases/involvement, at any time during the disease course, are excluded from the study.
Has known active central nervous system (CNS) involvement; subjects with previously treated CNS disease may participate provided they are stable (without evidence of CNS leukemia at the time of screening and any neurologic symptoms have returned to baseline) and are not using steroids for at least 7 days prior to trial treatment
Patients with metastatic central nervous system (CNS) tumors are allowed provided that they are clinically stable for a period of 30 days prior to study entry and there is not a requirement for steroid (other than close to physiologic doses) or anti-convulsant therapy; patients with leptomeningeal involvement are excluded
Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
For lymphodepletion chemotherapy, JCAR014 and durvalumab: Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
History of clinically manifested central nervous system (CNS) metastases, except if brain metastases have been treated, are stable and are asymptomatic
Clinical evidence of (parenchymal or meningeal) central nervous system (CNS) involvement or metastasis; in subjects suspected of having CNS disease, a magnetic resonance imaging (MRI) scan of the brain and lumbar puncture should be done to confirm
Patients with untreated or symptomatic metastatic central nervous system (CNS) disease; however patients with CNS involvement may participate if:\r\n* Clinically stable with respect to the CNS tumor at the time of screening and > 2 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment\r\n* Not on steroid therapy\r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)
Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed.
Active central nervous system (CNS) lymphoma within two weeks of registration; patients with a history of CNS involvement must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week; (otherwise lumbar puncture [LP] is not required if no clinical suspicion or evidence of CNS involvement); patients who have received cranial radiation therapy must still be eligible to receive total lymphoid irradiation to 7 Gy
At screening, patients with =< 3 CNS metastases and each =< 1 cm size that were treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 30 days after definitive treatment, and if the patients with CNS metastases are not taking prednisone > 10 mg or equivalent daily
At screening, patients with > 1 cm or > 3 in number treated CNS metastases may be included if there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, and if the patients with CNS metastases are not taking prednisone > 10 mg or equivalent daily
Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent steroid daily will be excluded
Patients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent steroid daily will be excluded
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent will be excluded
Patients with active central nervous system (CNS) involvement with malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
For patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day 1 of the study and meet the following criteria:\r\n* At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment with radiation to the CNS metastases\r\n* At least 14 days since last dose of corticosteroids\r\n* Must not have leptomeningeal disease or cord compression
Subjects with signs or symptoms indicative of CNS involvement; a CNS evaluation should be performed as clinically appropriate to rule our CNS involvement
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) are eligible for the study provided they are clinically stable and have met ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Patients with >= 5 white blood cells in the cerebrospinal fluid with blasts (CNS3) disease will be eligible if central nervous system (CNS) disease is responsive to therapy
CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1 to 2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then repeat imaging will be performed, if more than 4 weeks have elapsed from the last scan
Known active (untreated) central nervous system (CNS) metastases that require steroids; subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 2 weeks before study entry, defined as:\r\n* No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases\r\n* Asymptomatic and receiving either no or stable doses of anticonvulsants and total doses of corticosteroids equivalent to 10 mg of prednisone or less
Tumor lesions in the CNS are permitted but lesions must have been stable for at least 3 months prior to Cycle 1 Day 1 (C1D1). Stable CNS lesions are defined as not requiring steroid prophylaxis or other medications to prevent seizures or other complications associated with CNS lesions and no evidence of worsening of CNS disease.
In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of selinexor and sorafenib administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for cytotoxic/noncytotoxic agents; the use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled central nervous system (CNS) leukemia at the discretion of the PI and with the agreement of the sponsor; controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluations; (2) use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy; these medications will be recorded in the case-report form
PHASE II: At least one measurable extra-CNS lesion based upon RECIST version 1.1; Note: participants with at least one CNS lesion >= 10 mm but no other measurable extra-CNS lesions will still be allowed to participate
History of hemorrhagic CNS metastases
Relapsed/refractory leukemia in 2nd or greater relapse or who have failed at least one re-induction attempt after relapse or for refractory disease. Patients must meet the WHO classification with ? 5% blasts in the bone marrow or must have definitive extramedullary disease (e.g. chloromas, skin lesions). Patients may have asymptomatic CNS 1 or CNS 2 disease, but not CNS 3 or symptomatic CNS disease. OR
Relapsed/refractory non-CNS solid tumor that has not responded or has relapsed and for which no standard treatment is available. Patients may not have primary CNS tumors or CNS metastases. Lymphoma patients are permitted. Patients do not need to have measurable disease.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization
Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases are to be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
Known CNS metastases, unless stable and asymptomatic. Subjects with CNS metastases may be eligible for the study, provided:
There is no evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.
Patients with active or prior central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; NOTE: these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretion
Symptomatic CNS metastases or CNS metastases requiring steroids
Patients with recurrent or progressive AT/RT or MRT (either CNS and/or extra-CNS) with radiographically measurable disease as defined by at least one lesion that can be measured in two dimensions or with tumor cells present in the CSF taken within 2 weeks prior to enrollment
Subject has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Subjects with brain metastases may be eligible 2 weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.
Patients with central nervous system (CNS) 1 or CNS 2 disease are eligible; patients with isolated CNS relapse or CNS 3 disease are not eligible
Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
Uncontrolled CNS metastases
Patients with non central nervous system (CNS) primary tumors who have known brain metastases or symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic abnormality in the cerebrospinal fluid (CSF) should be excluded from this clinical trial; patients with metastatic CNS tumors will not be excluded from enrollment on this study in the phase I component only
Suspected, known, or progressive CNS metastases (Imaging required only if participants are symptomatic)
Participant has overt central nervous system (CNS) disease (CNS 3 status)
Subjects must either have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or if CNS metastasis is present, must have stable treated cerebral metastases from BC, NSCLC, RCC, CRC, GEC, or melanoma. Subjects must not have symptomatic auto-immune disease or be immunosuppressed.
Patients must not have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients with evidence of central nervous system (CNS) metastasis, spinal cord compression, or leptomeningeal disease within one year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
Concurrent systemic high-dose corticosteroids when used intermittently in an antiemetic regimen for central nervous system (CNS) metastases management or as a part of the premedication regimen are allowed
Untreated CNS disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease or symptoms.
Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior, or currently treated brain metastases are allowed.
Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for 2 weeks prior to Cycle 1 Day 1 will be eligible.
Known active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at the time of registration; prophylactic intrathecal chemotherapy is not a criterion for exclusion
Patients with known central nervous system (CNS) disease are allowed if there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to study drug administration; information obtained from standard of care historical data will be used for this purpose
Current CNS involvement by disease
ALK-positive NSCLC patients with asymptomatic central nervous system (CNS) metastases who are neurologically stable or have not required increasing doses of steroids within the 2 week prior to study entry to manage CNS symptoms
Non-ALK-positive NSCLC patients with CNS metastasis should have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids
Evidence of clinically significant central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing
Patients with symptomatic brain metastases are excluded; however, patients with asymptomatic central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior local treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery; patients receiving steroids for CNS metastases may not participate on this study
Concurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated; such treatment may continue until the planned course is completed; subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement
Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions)
Research participants with CNS involvement by leukemia, if deemed to be controlled and treatable by study team, at the time of enrollment are eligible; however, the CNS disease has to have been adequately treated with complete resolution of CNS leukemia confirmed by cerebral spinal fluid (CSF) analysis and imaging studies (if applicable) to be eligible to proceed with lymphodepletion
Patients with active CNS disease
Clinical evidence of active central nervous system (CNS) leukemia requiring active therapy; prior CNS leukemia well-controlled by ongoing therapy is allowed
Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ?1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
Patients with primary CNS tumors as well as patients with CNS metastases are excluded.
Active central nervous system (CNS) involvement by malignancy; Note: Patients with history of CNS disease that has been effectively treated will be eligible provided that treatment was > 4 weeks before enrollment
Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
Active central nervous system (CNS) disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma; a lumbar puncture demonstrating DLBCL at the time of registration to this study is not exclusion for study enrollment
Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
Patients with central nervous system (CNS) disease are eligible for treatment only after their CNS disease has been directly addressed with radiation therapy
If prior CNS leukemia, it must be treated and in CNS complete remission (CR)
Patients who have active central nervous system (CNS) disease; patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible
Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; NOTE: patients with treated CNS metastases without evidence of progression and without uncontrolled symptoms or need for steroids may enroll
Patients with active known CNS lymphoma. Patients with history of CNS leukemia now in remission are eligible for the trial.
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligible
Patients with stable and clinically insignificant central nervous system (CNS) disease are allowed; patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 month
Patients with known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:\r\n* No evidence of new or enlarging CNS metastasis\r\n* Off steroids that are used to minimize surrounding brain edema; patients with clinically insignificant brain metastases that do not require treatment are eligible
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment; prophylactic intrathecal medication is not a reason for exclusion
Have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
Have or do not have active (untreated or progressing) CNS metastases.
Active central nervous system (CNS) metastases; magnetic resonance imaging (MRI) (or computed tomography [CT]) required within 3 months of starting treatment for all tumor types known to commonly metastasize to the brain (i.e. all tumors except pancreas, colorectal, ovarian) and for all patients with CNS symptoms that may represent CNS metastases; metastases which have been treated with radiotherapy > 2 months prior to start of protocol therapy and are asymptomatic (off steroid therapy for at least 1 month) may be included; patients must have had normal or stable (if treated, no new lesions) brain imaging (CT or MRI) within the two months prior to day 1 of study drug\r\n* For the NSCLC expanded cohort only: radiation =< 14 days prior to day 1 of study drug; subjects must be off steroids for > 14 days prior to day 1 of study drug and anticonvulsants must be discontinued
Subjects who have metastasis to the brain are eligible for IV administration; however, any CNS lesion must be inactive; prior metastasis that has been treated and is no longer present is acceptable; no metastases to the CNS (brain or spine) of non-CNS solid tumors may be injected due to the potential for swelling at the injection site
All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study
Patients must be free of active or ongoing ischemic or degenerative CNS disease and no active or resistant CNS leukemia
Patients with a history of central nervous system (CNS) tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollment
Known CNS metastases or carcinomatous meningitis. Subjects with previously treated, stable CNS metastases (no evidence of progression for ? 4 weeks, and resolution of neurologic symptoms to baseline state) are permitted in this study.
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
Uncontrolled CNS metastases, primary CNS tumors, or solid tumors with CNS metastases as only measurable disease;
Patients with active central nervous system (CNS) lymphoma or active cerebrospinal fluid (CSF) involvement with malignant cells requiring CNS-specific therapy with IV or intrathecal (IT) methotrexate (MTX); Note: Patients with any prior CNS lymphoma (parenchymalor leptomeningeal) MUST be in complete remission (CR) in those compartments without any maintenance therapy required
Known central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.
Clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia
Active CNS metastases.
Presence of symptomatic or uncontrolled central nervous system (CNS) metastases requiring local CNS-directed treatment.
Patients with active, untreated central nervous system (CNS) metastases will be excluded from this clinical trial; patients who have brain metastases that been treated with radiation therapy or surgery will be required to have a washout period of at least 3 weeks prior to study entry, must be neurologically asymptomatic, and must not require systemic steroids
Patients with CNS metastases with the following exceptions:
Patient untreated CNS metastases with 4 or fewer sites of disease, with no single site larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays.
Patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent).
Evidence for active CNS involvement by leukaemia
Patients with symptomatic CNS metastases;
Patients diagnosed with primary central nervous system (CNS) or with CNS metastases or involvement, at any time during the disease course, are excluded from the study.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Patients with known CNS metastases (Patients with any clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least 3 weeks prior to randomization).
Patients with active CNS disease
Extramedullary (CNS) disease;
Patients with symptomatic CNS metastases.
History or clinical evidence of cnetral nervous system (CNS) HL
Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative computed tomography (CT) scan or negative diagnostic lumbar puncture prior to first dose
Known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they (1) have completed their treatment and have recovered from the acute effects of radiation therapy and/or surgery prior to enrollment, (2) have discontinued corticosteroid treatment for these metastases for at least 14 days, and (3) are neurologically stable;
210 Evidence of CNS involvement by NHL.
Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment\r\n** Screening CNS radiographic study ? 4 weeks from completion of radiotherapy and ? 2 weeks from discontinuation of corticosteroids
History or presence of clinically relevant CNS pathology
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to randomization\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 4 weeks prior to randomization.\r\n** Screening CNS radiographic study 4 weeks from completion of radiotherapy and 2 weeks from discontinuation of corticosteroids
If they have untreated central nervous system (CNS) metastasis; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trial
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required
Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.
Known active untreated CNS metastases and/or carcinomatous meningitis.
Active or symptomatic central nervous system (CNS) disease\r\n* For study purposes, a subject will not be considered as having active CNS disease if the subject has documentation of prior CNS disease and has received prior treatment (IT or radiation) and is:\r\n** Asymptomatic for the last 28 days prior to screening and\r\n** Has documented at least 2 negative cerebrospinal fluid (CSF) cytology (which must include 1 lumbar puncture [LP] within the study screening window)
Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
Symptomatic and/or untreated central nervous system (CNS) metastases; patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
Patients with seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for > 14 days
Symptomatic and/or untreated or actively progressing central nervous system (CNS) metastases or leptomeningeal disease. Patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:
Who have active central nervous system (CNS) disease; patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible
Patients with Gilbert's disease or known CNS metastatic disease. However, patients with CNS metastases who are asymptomatic and have completed a course of therapy are eligible for the study provided that they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new enlarging CNS metastasis, (2) off steroids or on a stable dose of steroids.
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy =< 28 days prior to registration\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation =< 28 days prior to registration\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Active and untreated central nervous system (CNS) metastases (including metastasis identified during screening MRI or contrast CT); patients with asymptomatic, treated metastases may be eligible if their lesion(s) have demonstrated stability over 2 months
Untreated brain metastases or neurologically unstable central nervous system (CNS) metastases (CNS metastases will be considered stable if there are no new nor enlarging lesions for one month, and the patient remains off steroids and anti-epileptics for the same time period)
Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required)
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n* Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Stratum 1: Recurrent or refractory primary malignant central nervous system (CNS) tumor patients \r\n* Patients with a histologically confirmed diagnosis of a primary malignant non-brainstem CNS tumor (excluding DIPG patients) that is recurrent, progressive, or refractory; all tumors must have histologic verification at either the time of diagnosis or recurrence except patients with marker (+) CNS germ cell tumors
Any active CNS metastases
Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.
Patients must have no history of central nervous system (CNS) metastasis at the screening assessment\r\n* NOTE: Patients with stable brain metastases (mets) which have been treated are eligible; patients with suspected symptoms of CNS metastasis should undergo CNS imaging at the time of screening to rule out active metastasis
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded
Patients with active or untreated central nervous system (CNS) disease; patients previously treated for CNS disease must be asymptomatic and must not be using steroids for at least 4 weeks prior to starting the study treatment
Patients with a history of ventral nervous system (CNS) myeloma or other CNS malignancy.
TUMOR BIOPSY SEQUENCING: Patients with history of central nervous system (CNS) metastases who have received treatment and who either have not had seizures or have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks will be eligible; enzyme-inducing anticonvulsants are contraindicated
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 3 months and must be off steroid treatment prior to study enrollment
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; NOTE: patients treated with stereotactic radiotherapy or surgery are eligible if no evidence of CNS disease progression >= 4 weeks and patients must be off corticosteroid therapy for >= 3 weeks; NOTE: carcinomatous meningitis is excluded regardless of clinical stability
Participants who have a primary central nervous system (CNS) malignancy, or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); individuals with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:\r\n* Evaluable or measurable disease outside the CNS\r\n* Radiographic demonstration of stability upon the completion of CNS directed therapy and no evidence of interim progression (for at least 4 weeks prior to the first dose of study drug) between the completion of CNS-directed therapy and the screening radiographic procedure\r\n* The screening CNS radiographic procedure is >= 8 weeks since completion of radiotherapy and >= 4 weeks since the discontinuation of corticosteroids and anticonvulsants\r\n* Note: These exceptions do not include carcinomatous meningitis which is excluded regardless of clinical stability
Patients with symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; exceptions include patients with previously-treated CNS metastases or those with are asymptomatic, subcentimeter metastases, and have no requirement for steroids or anti-seizure medication for at least one week prior to study entry; screening with CNS imaging studies (CT scan or MRI) is required
Patients with untreated malignant involvement of the central nervous system (CNS) should be excluded from this clinical trial; head imaging will be necessary to document absence of CNS involvement in patients with colon/rectal cancer and soft tissue sarcomas; patients with hematologic malignancies who have undergone treatment for malignant involvement of the CNS must have no evidence of residual disease by imaging or cerebrospinal fluid (CSF) sampling prior to study enrollment
Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
Has known active intraparenchymal lymphomatous central nervous system (CNS) lesions and/or lymphomatous meningitis; subjects with previously treated CNS involvement by lymphoma may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain lesions, and are not using steroids for at least 7 days prior to trial treatment
Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, use of steroids, or seizure disorder
Symptomatic leukoencephalopathy, active central nervous system (CNS) malignancy or other neuropsychiatric abnormalities believed to preclude transplantation (previous CNS malignancy, presently in complete remission [CR] is not an exclusion)
Patients with a history of prior central nervous system (CNS) metastases or skull lesions with intracranial extension will be required to have a head computed tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no active CNS metastases; patients with skull metastases with associated intracranial soft tissue masses will remain eligible
Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other\n             central nervous system (CNS) metastases are only permitted if treated, asymptomatic,\n             and stable (not requiring steroid for at least 4 weeks prior to the start of study\n             treatment). Cohort B only: Patients with CNS metastases or leptomeningeal\n             carcinomatosis are excluded.
Known active central nervous system (CNS) metastases or carcinomatous meningitis; patients with CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; however, oral corticosteroids for control of CNS symptoms are not allowed on study
Untreated central nervous system (CNS) metastasis; if treated CNS metastasis/es, treatment of CNS disease (surgery or radiation) must have been completed at least 30 days prior to registration; patients could still be on steroids
Patient with uncontrolled or symptomatic central nervous system (CNS) metastases; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy and are clinically stable and have discontinued prior treatment with anticonvulsants
Patients with CNS involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion ((including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
Patients with asymptomatic untreated CNS disease may be enrolled after consultation, provided all of the following criteria are met:\r\n* Evaluable or measurable disease outside the CNS\r\n* No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n* No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1
Patients with asymptomatic treated CNS metastases may be enrolled after consultation, provided all the criteria listed above are met as well as the following:\r\n* Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n* Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Central nervous system (CNS) function defined as:\r\n* Patients with seizure disorder may be enrolled if on allowed anti-convulsants and well controlled; benzodiazepines and gabapentin are acceptable\r\n* CNS toxicity =< grade 2
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Subject has symptomatic/untreated CNS disease
Patients with a history of central nervous system (CNS) leukemia must be stable, off steroids, with clear cerebrospinal fluid (CSF) for > 3 months prior to day 1 of Erwinaze administration (patient can receive monthly intrathecal maintenance chemotherapy)
Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression)
Patients with refractory or recurrent solid tumors or lymphomas, excluding CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse; patients with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible
Patients with primary CNS tumors are not eligible
Patients with prior history of or known metastatic CNS disease involvement are not eligible; (Note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated)
Patients who have a known primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment
Patients with central nervous system (CNS) involvement may participate if the patient is:\r\n* >= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapy
Stage 1 solid tumor and stage 2 endometrial and ovarian cancer participants with known central nervous system (CNS) metastatic lesions which are symptomatic and/or growing; patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll; brain metastasis must be stable for 1 month with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases); CNS imaging will not be mandated for asymptomatic patients with no history of CNS metastases
Extradural masses that have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible; patients with previous central nervous system (CNS) tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible; patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits and no progression of residual brain abnormalities without specific therapy, are eligible one week post radiation or radiosurgery; patients with asymptomatic sub-centemeric CNS lesions will be eligible if no immediate radiation or surgery indicated
Known active central nervous system (CNS) leukemia or lymphoma – patients with previously treated CNS disease are permitted if neurologically stable with no ongoing or anticipated need for steroid therapy are eligible
A prospective patient for allogeneic hematopoietic stem cell transplant (HSCT) for hematologic conditions, both malignant and non-malignant; donor can be unrelated marrow or peripheral blood cells; a patient with history of central nervous system (CNS) involvement is eligible if CNS disease is in remission at time of study consideration
Leptomeningeal carcinomatosis as only site of CNS disease
At screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment
Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded
Patients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excluded
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy
At screening, patients with =< 3 treated CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment
Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded
Patients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excluded
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy
Patients with central nervous system (CNS) metastases or a history of CNS metastases are ineligible
PHASE II: Patients with CNS metastases or a history of CNS metastases are ineligible
Patients who have a primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment
Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: \r\n* CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs); \r\n* CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm\r\n* CNS3 with marrow disease who has failed salvage systemic and intensive intrathecally (IT) chemotherapy (and therefore not eligible for radiation)\r\n* Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy)
Patients with active CNS metastases
History or clinical evidence of central nervous system (CNS) tumor involvement\n             (metastases) or other known clinically relevant CNS pathology (e.g., epilepsy,\n             seizure, paresis, aphasia, cerebellar disease, severe brain injury, psychosis).
Patients with active central nervous system (CNS) metastases are excluded; patients with CNS metastases that have been treated must be off steroid treatment for > 2 months and be asymptomatic; patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRI
Untreated central nervous system (CNS) metastases or symptomatic CNS metastases requiring escalating doses of corticosteroids
Active central nervous system (CNS) malignancy as defined by:\r\n* Lymphoma: tumor mass on computed tomography (CT) scan or leptomeningeal disease\r\n* Leukemia: CNS 2 or CNS 3 classification
Patients with CNS progression during the trial will be allowed to receive local treatment for CNS metastases and will remain on protocol; trial medications will be held during the time patients are receiving radiation therapy as dictated by their treating physicians
Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures or history of seizures, and/or any CNS metastases are ineligible
Patients with central nervous system (CNS) tumors or known CNS metastases are not eligible; patients with a history of CNS metastases that have been surgically resected are eligible only if the baseline evaluation shows no evidence of current CNS metastases; patients with any evidence of CNS metastases on baseline evaluation are not eligible, regardless of whether the lesions have been previously treated and/or appear stable
Patients with a history of central nervous system (CNS) involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible; patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment
Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment with surgery, radiation or both; in addition, they must be off corticosteroids
Active CNS metastases or carcinomatous meningitis
Subjects with symptomatic CNS metastases.
Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
Subjects with untreated CNS metastases are excluded.
Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
Active CNS metastases or leptomeningeal disease.
CNS metastases
Known CNS metastases or leptomeningeal disease: For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or surgery who are considered stable by CNS imaging and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled. For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are not eligible. However, such patients with other forms of CNS-3 leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least 3 months prior to CTL019 infusion. Patients must have no acute/ongoing neurologic toxicity > Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 3 months.
Patients with untreated or symptomatic metastatic central nervous system (CNS) disease; however patients with CNS involvement may participate if:\r\n* Clinically stable with respect to the CNS tumor at the time of screening and > 4 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment\r\n* Not receiving steroid therapy \r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)
Known symptomatic central nervous system (CNS) metastases. Participants with a history of treated or untreated asymptomatic CNS metastases may be eligible.
Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma
Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.
Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy completion to starting the study treatment and has stable CNS tumor at time of screening and not receiving steroids and/or enzyme inducing ant-epileptic medications for brain metastases
Radiological evidence of CNS metastases
Symptomatic, untreated CNS metastases
Has active central nervous system (CNS) metastases (including evidence of cerebral edema by MRI, or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment.
Has known active CNS metastases and/or carcinomatous meningitis.
Subject has primary central nervous system (CNS) tumor or known CNS metastases and/or history of CNS metastases and/or carcinomatous meningitis; Exception: Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be off corticosteroids for 4 weeks prior to enrollment.
Subjects who have had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma, or plasma cell leukemia
Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]) a. Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well-controlled and stable for at least 28 days after receiving local therapy (irradiation, surgery, etc.)
Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.
CNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
Active signs or symptoms of CNS involvement by malignancy
Has known active CNS metastases and/or carcinomatous meningitis.
Subjects who have had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
Patients who have central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* >= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, except ATRT
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
No known central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretion; intrathecal (IT) methotrexate or IT cytarabine prophylaxis in patients with negative CSF who are felt to be at high risk of CNS relapse is allowed per local MD discretion; this should be noted on the treatment form
Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
Patients with primary CNS tumor or CNS tumor involvement
Evidence of CNS involvement with DLBCL
CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
Known brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for 4 weeks.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
Patients with CNS malignancies (primary or metastatic)
Patients with a history of treated brain metastases should be clinically stable for ? 4 weeks prior to signing the informed consent. Glucocorticoid therapy for central nervous system (CNS) edema is permitted if ? 20 mg of prednisolone (or equivalent).
Patients with CNS metastases that are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before pre-registration. Asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications are eligible after discussion with the sponsor medical monitor. For patients with a history of CNS metastasis, baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
Carcinomatous meningitis and/or symptomatic CNS metastases
Patients with a prior diagnosis of CLL/SLL in central nervous system (CNS) are eligible only if the CNS disease has been treated; patients must be neurologically stable, without progressive symptoms while off of steroids and anti-convulsants; at least 28 days must have elapsed since CNS treatment, and the patient must have recovered from all associated toxicities of treatment; patients who have transfusion-dependent thrombocytopenia or bleeding/coagulation disorders that may increase the risk of life-threatening bleeding are excluded
A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of the CNS. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS.
Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease\r\n* Note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed > 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
Patients with known brain metastasis are eligible only if by central nervous system (CNS) imaging there is no evidence of CNS progression at least 30 days following definitive CNS treatment (resection or radiation)
Patients with central nervous system 3 (CNS3) leukemia\r\n* CNS status must be known prior to enrollment; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); B-LLy patients with CNS3 disease are not eligible for this protocol or the COG HR ALL protocol; it is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; this is allowed prior to registration; systemic chemotherapy must begin within 72 hours of the first dose of intrathecal therapy
At least one prior treatment to a central nervous system (CNS)-based lesion is required; prior therapy must be completed > 2 weeks prior to enrollment; a previously treated lesion must be demonstrated by MRI to have progressed following treatment in order to be eligible; the subsequent development of a new CNS lesion that was not previously treated will be permitted and does not require treatment followed by progression prior to enrollment; treatment of a single CNS lesion with local therapy in the context of multifocal disease is permitted as long as at least one untreated lesions meets criteria for measurable disease; patients should have received minimum of one line of systemic therapy
CNS disease other than neurologically stable, treated brain metastases.
History of, or known central nervous system (CNS) involvement caused by the underlying B-cell malignancy or prior history of National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) Grade greater than or equal to >= 3 drug-related CNS toxicity. Participants with signs or symptoms of CNS involvement should have a computed tomography (CT) or magnetic resonance imaging (MRI)
CNS metastasis that is symptomatic or progressing or untretaed or that required current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases)
Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion to starting the study treatment and have stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases
Known uncontrolled or symptomatic CNS metastases
Patient with CNS metastases.
Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
Symptomatic or untreated central nervous system (CNS) leukemia. Subjects are permitted to enroll if previously treated for CNS disease, free of symptoms at the time of screening, and have not required intrathecal chemotherapy at least 1 month prior to study Day 1.
Have the presence of unstable central nervous system (CNS) metastasis. History of CNS metastasis or stable CNS metastases is allowed (no longer requiring active therapy such as steroid medications). Participants with a history of CNS metastases must have a brain scan (for example, magnetic resonance imaging [MRI]) within 28 days of randomization to document stability, even if there have been no changes in symptoms.
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or radiation therapy and with confirmed stable disease (SD) for >= 3 weeks are allowed
History or evidence of CNS disease. Radiographic screening of all participants without history of CNS metastasis is required.
Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
Known uncontrolled or symptomatic CNS metastases
Patient with known central nervous system (CNS) metastasis (radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patient is asymptomatic, and no steroids have been administered for at least 30 days)
Participants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease status
Known primary central nervous system (CNS) malignancy, active or untreated CNS metastases, symptomatic CNS metastases, and/or leptomeningeal disease
Known active or suspected brain or leptomeningeal metastases. CNS imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement. Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 8 weeks following radiation therapy or other locoregional ablative therapy to the CNS.
Have untreated central nervous system (CNS) metastases. Patients are eligible for study participation if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 60 days prior to consent. In addition, patients must either be off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 60 days prior to consent.
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy within prior 2 weeks.
Active and/or untreated CNS disease or non-stable brain metastases
Have active leukemic central nervous system (CNS) involvement, as defined by any leukemic blasts detected in the cerebrospinal fluid (CSF) by morphology or flow cytometry and/or any chloromas detected by CNS imaging
Presence of CNS-3 disease and CNS-2 disease with neurological changes
Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to Study Day
Asymptomatic and adequately treated CNS metastases are not exclusionary
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded
Patients with central nervous system (CNS) involvement may participate if they meet all the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening
Patients with central nervous system (CNS) involvement unless they meet all of the following criteria: a. At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment. b. Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or radiation therapy and with confirmed stable disease (SD) for >= 2 weeks are allowed
Known untreated central nervous system (CNS) metastases; Note: patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for this purpose =< 30 days prior to randomization
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registrations and do not require corticosteroids (of any dose) for symptomatic management
Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases
Have symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.
History of central nervous system (CNS) metastases unless previously treated and stable for > 8 weeks prior to study initiation
Uncontrolled central nervous system (CNS) metastases; patients are considered to have controlled CNS metastases (and thus eligible) if they have completed local therapy (radiotherapy [XRT] and/or surgery) and are off steroids with clinical and radiographic stability 1 month from the end of CNS-directed therapy
Diagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessment
Participant with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis Participants with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) ? 28 days (? 14 days for stereotactic radiosurgery) and, if on corticosteroid therapy, should be receiving a stable dose of no greater than 4 mg/d dexamethasone (or equivalent anti-inflammatory potency of another corticosteroid) for at least 14 days before start of study treatment). Patients must not be receiving corticosteroids for brain metastases.
Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
Has known active central nervous system (CNS) lymphoma and/or lymphomatous meningitis; subjects with previously treated CNS lymphoma and/or lymphomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
Subjects with active central nervous system (CNS) metastases are excluded; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks
Untreated central nervous system (CNS) metastasis that are > 1 cm or symptomatic are not allowed; (patients with CNS metastases > 1 cm or symptomatic that have been treated and demonstrated to be radiologically and clinically stable for at least 4 weeks are allowed)
Leptomeningeal carcinomatosis or other untreated or symptomatic central nervous system (CNS) metastases; patients with asymptomatic CNS metastases, other than leptomeningeal disease, are eligible provided they have been clinically stable without requiring increase in steroid dose for at least 4 weeks
History of brain metastases; EXCEPTION: patients with a solitary brain metastasis that has been completely resected, and who have no ongoing central nervous system (CNS) symptoms and an MRI documenting no evidence of CNS disease at least 3 months after resection and within 30 days of registration, are eligible for treatment
Patients must have previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease
Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ? 3 months.
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is receiving low dosage corticosteroid therapy
Uncontrolled central nervous system (CNS) metastases\r\n* NOTE: metastases have been treated by surgery and/or radiotherapy and patients have been neurologically stable and off of steroids > 12 weeks are eligible
Unstable CNS metastases or leptomeningeal carcinomatosis not considered radiographically stable
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Patients with active central nervous system (CNS) malignancy\r\n* Asymptomatic small lesions are not considered active\r\n* Treated lesions may be considered inactive if they are stable for at least 3 months
Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months; patients with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included
CNS metastases that are symptomatic and /or requiring escalating doses of steroids.
Known active CNS metastases and/or carcinomatous meningitis
Patients with central nervous system (CNS) involvement may participate if the patient meets all of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapy\r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases
Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ?1 month are eligible.
No signs or symptoms of CNS metastases (mets) within the last 30 days (from enrollment evaluation)
CNS disease:
Dose escalation and MTD/RP2D expansion cohort: Patients with symptomatic CNS metastases are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS metastases not requiring immediate local therapy may be eligible. Enrollment of patients with metastases must be approved by the study medical monitor.
Optional CNS disease expansion cohort: Patients with asymptomatic untreated CNS metastases not needing immediate local therapy or patients with progressive CNS disease following local therapy may be eligible with medical monitor approval.
Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression for at least 4 weeks prior to screening, have no evidence of new or enlarging brain metastases, and are off steroids for at least 7 days before first dose of pembrolizumab.
Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible.
Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL
History of or current relevant CNS pathology
Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
Evidence of untreated CNS metastases
PART B: Patients with CNS metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessments
Leptomeningeal carcinomatosis as the only site of CNS involvement
Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy); brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients
Patients with central nervous system (CNS) involvement may participate if:\r\n* Clinically stable with respect to the CNS tumor at the time of screening and > 4 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment\r\n* Not receiving steroid therapy\r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)
No clinical evidence of central nervous system (CNS) metastases (including carcinomatous meningitis) at baseline, with the exception of those patients who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) had no requirement for steroids or enzyme-inducing anticonvulsants within 6 months prior to registration
Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.
Patients with symptomatic brain or spinal cord metastases or requiring steroid therapy and patients with leptomeningeal disease; patients with treated and stable central nervous system (CNS) metastasis for 3 months or more, off steroids are eligible for the study; no major surgery or radiation therapy within 21 days before starting treatment
Patients with known central nervous system (CNS) metastases, unless metastases are treated and stable and the patients do not require systemic steroids
History of central nervous system (CNS) metastasis; Note: participants without clinical signs and symptoms of CNS involvement are not required to have magnetic resonance imaging (MRI) of the brain; (exception: participants with treated brain metastases who are asymptomatic, not currently on steroid therapy, and clinically stable for >= 2 weeks will be eligible for protocol participation)
Active central nervous system (CNS) disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease.
Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
Any untreated CNS metastases
Patient with symptomatic or growing CNS metastatic lesions
Patients with active central nervous system (CNS) involvement with malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukaemic CNS involvement (no lumbar puncture required, clinical assessment per investigator´s judgement is sufficient).
Brain metastases (unless stable disease >3 mos. by scan without additional CNS-directed therapy)
Active central nervous system (CNS) leukemia within two weeks of registration; patients with a history of CNS leukemia must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week; patients who have received cranial radiation therapy (XRT) must still be eligible to receive total body irradiation to 4 Gy
Clinical evidence of active CNS leukemia
Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ?10mg daily prednisone (or equivalent)
Any Central Nervous System (CNS) metastases or history of CNS metastases
History or evidence upon physical/neurological examination of central nervous system (CNS) disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures); symptomatic CNS metastasis
Active central nervous system (CNS) disease\r\n* Subjects with a history of CNS metastases or cord compression are allowable if they have been clinically stable for at least 6 weeks since completion of definitive treatment, are off steroids (if the steroids were part of the CNS disease treatment), and in the case of brain metastases, have stable or improved imaging at least 6 weeks after completion of their definitive treatment
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to registration; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Active CNS metastases
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases
Presence of symptomatic CNS lymphoma
Patients with central nervous system (CNS) progression are ineligible until this CNS progression is treated either with whole brain radiation or stereotactic radiosurgery (SRS) and have an magnetic resonance imaging (MRI) of the affected CNS lesion(s) 3 months after radiation therapy (per National Comprehensive Cancer Network [NCCN] guidelines) demonstrating stable (or improved) disease prior to proceeding with enrollment on the AVX901 study; patients also must be off all steroids prior to initiating the AVX901 protocol
For cohorts 1 and 3a/3b, patients must have new or progressive measurable central CNS lesions, as assessed by the patient's treating physician; this includes patients who have progressed after at least one line of standard treatment for CNS disease (whole brain radiotherapy [WBRT], stereotactic radiosurgery [SRS], or surgical resection as below)
In cohort 2, eligible patients will include those who have CNS disease that is amenable for surgery (typically < 3 brain metastases and with planned resection by neurosurgery); these patients may include those who have received or not received previous treatment(s) for their CNS
Those with leptomeningeal metastases as the only site of CNS disease
Cohort 2: Participants must have progressive disease in CNS or non-CNS sites
Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.
Known central nervous system (CNS) metastases or leptomeningeal carcinomatosis; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if the subject has clinical findings suggestive of CNS metastasis
Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy; direct biopsy of central nervous system (CNS) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent; patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy
Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesions
Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to treatment
Symptomatic brain or central nervous system (CNS) metastases; previously treated and stable CNS disease is allowed
Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
Patients with known prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
Patient has known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; oral corticosteroids for control of CNS symptoms are allowed
Symptomatic CNS disease
Brain metastases permitted in Arms A and B if:\r\n* Central nervous system (CNS)-directed treatment has been given\r\n* No CNS-directed therapy for the past 3 months, including glucocorticoids AND\r\n* CNS disease has been clinically and radiographically stable for at least 8 weeks
Patients must not have known central nervous system (CNS) metastases or leptomeningeal disease; screening with brain imaging is not required for asymptomatic patients
Distant metastases, including CNS and vertebral or meningeal involvement
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ? 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
Central nervous system (CNS) inclusion criteria:\r\n* Subjects without CNS metastases are eligible; Note: brain imaging is not required for asymptomatic subjects without known brain metastatic disease prior to enrollment into the study\r\n* Subjects with untreated asymptomatic CNS metastases not needing immediate local therapy in the opinion of investigator are eligible; for subjects with untreated asymptomatic CNS lesions > 2.0 cm magnetic resonance imaging (MRI), discussion with and approval from the lead principle investigator (PI) is required prior to enrollment\r\n* Subjects with stable brain metastases previously treated with radiation therapy or surgery are allowed to enroll, provided that they are off corticosteroids or on stable/tapering dose of corticosteroids and stability of CNS metastatic disease for at least 4 weeks has been demonstrated, with the last MRI taken within 2 weeks prior to cycle 1 day 1 of the study; relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of enrollment; prophylactic intrathecal medication is not a reason for exclusion
No active CNS disease
Patients with active brain metastases, or with a history of any central nervous system (CNS) metastases or cerebrospinal fluid malignant cells\r\n* Note: patients who are asymptomatic but are found to have malignant cells in the cerebrospinal fluid (CSF) on lumbar puncture prior to treatment will be considered eligible
Substantial central nervous system (CNS) disease including\r\n* History of CNS bleeding\r\n* Mass lesions in the brain\r\n* Uncontrolled seizure disorder\r\n* Recent history of cerebrovascular accident (CVA) (e.g. within the past 6 months)
Known or clinically suspected CNS involvement
Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease)
Untreated central nervous system (CNS) metastases or CNS metastases that have progressed after completion of radiotherapy.
Active, untreated CNS metastases.
Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well controlled prior to screening (as assessed by the Investigator) after receiving local therapy (irradiation, surgery, etc.)
Patients with known brain metastases diagnosed within 1 year will be excluded from this clinical trial; exception: patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS progression-free for the 1-year period
Symptomatic CNS metastases or evidence of leptomeningeal disease.
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusion
Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and must be off steroids for at least 4 weeks prior to enrollment
Patients with diagnosis of retinoblastoma with metastasis to the central nervous system (CNS) must be confirmed by an ophthalmologist and/or a pathologist; in conjunction with the pediatric oncologist; metastasis to the CNS is defined as a mass in the chiasm or other site in the CNS, confirmed by magnetic resonance imaging (MRI)\r\n* At diagnosis\r\n* At relapse after conventional therapy\r\nIt is acceptable to have other sites of metastatic disease: lymphatic, bone, bone marrow or others, but these will not be considered for response
Patients with metastatic to CNS with only cerebral spinal fluid (CSF) involvement are NOT ELIGIBLE
Patients may have CNS 1, 2 or 3 disease.
Patients may have CNS 1 or CNS 2 disease but not CNS 3.
Participants with untreated CNS metastases are excluded
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases is eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring systemic steroids and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 1 week prior to study drug administration.
Patients with asymptomatic CNS metastases are allowed
Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases. Treated and stable CNS metastases are allowed.
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Patients with untreated (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Subject has symptomatic central nervous system (CNS) metastasis. Subjects with asymptomatic, untreated CNS metastases are allowed. Subjects with previously treated and currently asymptomatic CNS metastases are eligible provided they meet the following:
Symptomatic central nervous system (CNS) lesions, or CNS lesions that require therapy
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Subjects with symptomatic or unstable CNS metastases
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy
Known active central nervous system (CNS) metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to study entry, defined as:
No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.
Known Central Nervous System (CNS) lymphoma; subjects with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusion; patients with known brain metastases should be excluded from this clinical trial
Patients with tumor involvement of the Central Nervous System (CNS). SCLC patients with previously treated CNS lesions must have stable CNS disease for at least 4 weeks
Central nervous system (CNS) metastases, with the following exception: Subjects who have previously treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug; Subjects with carcinomatous meningitis are excluded regardless of clinical stability.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for more than 1 week within 6 months prior enrollment
Untreated central nervous system (CNS) metastatic disease as defined by:\r\n* Solid tumors: history of untreated metastatic CNS tumor involvement; extradural masses which have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible; patients with previous CNS tumor involvement are eligible IF the CNS tumor(s) has been treated and has been stable or resolving for at least 4 weeks; and if the patient does not currently require steroids
Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ? 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;
Patients with central nervous system (CNS) metastasis. Intrathecal chemotherapy is allowed for patients who require CNS prophylaxis or therapy.
Known, uncontrolled CNS metastases
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug
Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scan
Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation
Patients with uncontrolled CNS tumor metastatic involvement
Known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging; a lumbar puncture is not required unless CNS involvement is clinically suspected; patients with signs or symptoms of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment
Have CNS lesions that are confirmed to be stable or regressing on imaging since the time of the last CNS treatment including the pre-treatment CT or MRI scan for this trial.
Patients having Central Nervous System (CNS) metastases. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed
Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:\r\n* Presence of measurable or evaluable disease outside of the CNS;\r\n* Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study\r\n* Completion of radiotherapy >= 8 weeks prior to the screening radiographic study\r\n* Discontinuation of corticosteroids and anticonvulsants >= 4 weeks prior to the screening radiographic study
Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion.
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms
Has known active CNS metastases and/or carcinomatous meningitis.
Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria:\r\n* Presence of measurable disease outside the CNS\r\n* No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed)\r\n* Absence of leptomeningeal disease
Patients with untreated central nervous system (CNS) metastases; patients with treated CNS metastases who are off steroids are eligible
Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:\r\n* Presence of measurable or evaluable disease outside of the CNS;\r\n* Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study;\r\n* Completion of radiotherapy >= 8 weeks prior to the screening radiographic study;\r\n* Discontinuation of corticosteroids and anticonvulsants >= 4 weeks prior to the screening radiographic study
Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
Brain metastases are excluded unless treated and shown to be controlled more than 1 month from after craniotomy or more than 2 weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and is in remission; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocol
Untreated or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases may be eligible
Patient with active CNS disease.
Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 28 days.
Patient with symptomatic brain metastases, ie, not neurologically stable or requiring treatment with corticosteroids, or central nervous system (CNS) leukemia.
Patient has symptomatic brain metastases, ie, presence of neurological symptoms or requiring treatment with corticosteroids, or CNS leukemia.
Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases
Known clinically active CNS leukemia
Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks)
Known, clinically suspected, or history of CNS tumor involvement.
Symptomatic or untreated central nervous system (CNS) metastases; patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: no evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy; no ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed; completed stereotactic radiation at least 1 week prior to cycle 1, day 1 or whole-brain radiation at least 2 weeks prior to cycle 1, day 1
Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging; a lumbar puncture is not required unless CNS involvement is clinically suspected; patients with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment
Subject has symptomatic central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination. Subject with prior brain metastases must:
A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months; patients with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included
Has untreated or uncontrolled CNS metastases, including patients who require glucocorticoid therapy for CNS metastases
If prior central nervous system (CNS) leukemia, it must be treated and in CNS complete remission (CR)
Clinical evidence of active CNS leukemic involvement
Patients has primary CNS tumor or CNS tumor involvement
Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
Persistent and/or recurrent cervical cancer o No CNS/spinal metastases
Patients with CNS 3 disease or symptomatic CNS disease
Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement
Active, untreated CNS metastases
Active ALL in the CNS or testes
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or stereotactic radiosurgery and with confirmed stable disease (SD) for >= 2 weeks are allowed
Has untreated or uncontrolled central nervous system (CNS) metastases, including patients who require glucocorticoid therapy for CNS metastases
Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone =< 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatment
Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
No 'active' CNS metastases. Prior CNS metastases are allowed, provided adequate palliative therapy has been administered and CNS disease control has been established prior to study entry. • A brain MRI scan, ? 28 days from day 1, is required
CNS metastases that are symptomatic and /or requiring steroids.
History of central nervous system (CNS) hemorrhage or thrombosis; patients with a history of CNS lymphomatous involvement are eligible only if their CNS disease is in remission at the time of study entry
Evidence of current CNS involvement.
Known, uncontrolled CNS metastases or primary CNS lymphoma
Symptomatic or untreated central nervous system (CNS) metastatic disease. Patients with previously treated CNS metastatic disease which has been stable for at least 56 days are eligible
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: \r\n* No evidence of new or enlarging CNS metastasis \r\n* Off steroids that are used to minimize surrounding brain edema
Patients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
Symptomatic CNS disease
No known central nervous system (CNS) metastases or neurological symptoms possibly related to active CNS metastasis
Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required
CNS metastases.
The patient has known active or suspected central nervous system (CNS) leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
For subjects with solid tumors that are not primary central nervous system (CNS) tumors or NF-1 associated plexiform neurofibromas subjects with symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression are excluded. NOTE: Subjects previously treated for these conditions that have had stable CNS disease (verified with consecutive imaging studies) for >3 months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose or decreasing of corticosteroids for at least 7 days prior to enrolment are permitted.
Known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed)
Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)
For participants with leukemia, has overt central nervous system (CNS) disease (CNS 3 status).
Symptomatic CNS metastases
If prior central nervous system (CNS) leukemia, it must be treated and have no evidence of CNS disease
Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.
Patients with asymptomatic central nervous system (CNS) metastases will be eligible; for patients that have undergone radiation therapy for their CNS metastases, a minimum of 14 days must elapse prior to study registration, and patients must have recovered from any adverse events related to radiotherapy with the exception of alopecia and grade 1 neuropathy
Primary central nervous system (CNS) malignancy or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
Evidence of CNS or leptomeningeal metastases
Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
Primary CNS tumor or CNS tumor involvement
Patients must be without clinical evidence of central nervous system (CNS) disease; patients with a history of treated brain metastasis must be stable with no evidence of disease for 3 months
Recipient must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous CNS tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain.
Newly identified CNS malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy please refer to Section 6.3 for allowed steroid maintenance therapy.
Presence of CNS involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical Monitor
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug.
Presence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapy
Presence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapy
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including [incl.] radiation and/or surgery), is clinically stable at the time of study entry, and is not receiving corticosteroid therapy
Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
Untreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: evaluable or measurable disease outside the CNS, radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study, and screening CNS radiographic study is >/= 8 weeks since completion of radiotherapy and >/= 4 weeks since the discontinuation of corticosteroids and anticonvulsants
Subjects with primary central nervous system (CNS) tumors or metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible providing they meet all of the following criteria: a) residual neurological symptoms grade ? 1; 2) no dexamethasone treatment; and c) follow-up MRI shows no new lesions appearing
Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.
Symptomatic CNS metastases
Symptomatic CNS metastases
Symptomatic CNS metastases
Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for subjects who have previously treated CNS metastases (surgery with or without radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria:\r\n* Are asymptomatic and,\r\n* Have had no clinical evidence of active CNS metastases for >= 28 days prior to enrollment and,\r\n* Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
The patient was diagnosed with leukemic Central Nervous System (CNS) disease (e.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement.
Patients with a history of central nervous system (CNS) metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidence by stable clinical findings and stable radiographic findings for a period of 6 weeks
Patients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks
Patients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks (cohort 2)
Patients may have had prior central nervous system (CNS) metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by computed tomography [CT] or magnetic resonance imaging [MRI])
Patients who have untreated (primary) or uncontrolled Central Nervous System (CNS) (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Clinical evidence of active CNS leukemic involvement
Patients with a history of CNS (central nervous system) leukemia are eligible if they are not symptomatic from current CNS involvement; if there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly with intrathecal chemotherapy per the treating physician
Central nervous system (CNS) metastasis; NOTE: history of brain metastasis other than locally treatable lesions (i.e., lesions treatable with surgery or radiosurgery); patients with locally treatable disease may be considered for study if they have completed treatment without evidence of CNS progression for > 4 weeks after completion of treatment; patients with a history of brain or other CNS metastases not amenable to local therapy will not be eligible
Patients with documented central nervous system (CNS) ischemia and/or infarction, whether symptomatic or discovered incidentally without clinical symptoms, will be excluded from study participation
In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of ponatinib administration will be at least 2 weeks for cytotoxic agents OR at least 5 half-lives for cytotoxic/non-cytotoxic agents; use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first eight weeks on study therapy from the day of enrollment, either prior to or concomitantly with ponatinib administration initially to control the peripheral blast count; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted; controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluations
Patients must have the status of central nervous system (CNS)1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 1 week prior the first dose of study drug.
Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 monthly time interval
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; however, patient treated with stereotactic radiotherapy, whole brain radiation or surgery are eligible if patient remained without evidence of CNS disease progression >= 4 weeks; patients must be off corticosteroid therapy for >= 2 weeks
Known untreated central nervous system (CNS) metastasis; patients with CNS metastasis will be allowed on study once treated
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery).
Have symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastases
Symptomatic CNS metastases
Central nervous system (CNS) metastases, with the following exception: • Subjects who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug. Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
Patients with prior history of primary central nervous system (CNS) cancer or CNS metastases
Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg
Comorbidities at particular risk (i.e., active central nervous system [CNS], active CNS metastases, hydrocephalus or coagulopathy)
History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out extramedullary CNS involvement;
Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.
Patients with central nervous system (CNS) lymphoma are not eligible for the trial unless the disease had been treated and the subject remains without symptoms with no active CNS lymphoma.
Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
Uncontrolled metastases to the central nervous system (CNS). Participants with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 4 weeks after definitive therapy and have not used steroids for at least 4 weeks prior to first dose of ABBV-085.
CNS lesions: A) Patients with CNS parenchymal or meningeal-based lesions that are present at study entry are NOT eligible due to concerns regarding toxicity attribution. B) Who have active CNS disease or a history of cranial irradiation are excluded due to concerns regarding toxicity attribution. Patients with previously treated leptomeningeal disease or brain metastases without evidence of remaining tumor by PET, MRI scan, or spinal fluid will be eligible; however such patients currently taking steroids as prophylaxis against seizures are not eligible.
Patients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is: \r\n* > 4 weeks from prior therapy completion (including radiation and/or surgery)\r\n* Clinically stable with respect to the CNS tumor at the time of study entry \r\n* Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement\r\n* Not receiving anti-convulsive medications (that were started for brain metastases)
Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening (within 28 days before C1D1) and prior radiographic assessments. Participants with radiographically stable, asymptomatic previously irradiated lesions are eligible provided participant is >= 4 weeks beyond completion of cranial irradiation and >= 3 weeks off of corticosteroid therapy. Participants with metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm) are completely excluded
History of central nervous system (CNS) disease, CNS radiation, intrathecal therapy, or CNS surgery
Exclusion criteria include previous central nervous system (CNS) radiation or CNS tumors that in the judgment of the investigators are likely to undergo progression during or shortly after radiotherapy
Patient has symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Patients who received prophylactic CNS treatment are eligible
Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, or CNS leukemia
Patients with active central nervous system (CNS) metastasis and/or carcinomatous meningitis; however, patients with CNS metastasis (except leptomeningeal disease) who have completed a therapy and are clinically stable for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants may be eligible
Subjects with active CNS or cerebrospinal fluid (CSF) involvement by malignancy
Patients must not have a history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Known central nervous system metastases causing clinical symptoms or metastases that require therapeutic intervention. Subjects with a history of treated central nervous system (CNS) metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening that do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is indicated, should be discussed with the Sponsor Medical Responsible
Subjects must not have a history of clinically manifested central nervous system (CNS) metastases. a. Subjects with known or suspected leptomeningeal disease or cord compression are not eligible.
Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: measurable disease outside the CNS, only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord), no evidence of progression or hemorrhage after completion of CNS-directed therapy, no ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed), no stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible for the trial if: a. the metastases have been treated by surgery and/or radiotherapy, b. the subject is off corticosteroids (>10 mg/day) and is neurologically stable for at least 2 weeks prior to Screening. c. brain MRI completed within 3 months of Screening.
Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases -- defined as metastasis having no evidence of progression or hemorrhage after treatment for at least 2 weeks
Known central nervous system (CNS) metastasis; once CNS metastasis have been treated these patients may participate if they are otherwise good trial candidates
Have known active uncontrolled or symptomatic CNS metastases
Have symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable does of steroids for ? 4 weeks prior to enrollment.
Participants with a history of CNS metastases are eligible provided they are stable and meet the criteria details in the protocol.
Has known active CNS metastases and/or carcinomatous meningitis.
Patients who have a history of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, psychosis, or other significant CNS abnormalities; a history of treated CNS leukemia will be allowed if recent CNS studies confirm the absence of active CNS disease at the time of study entry (screening)
Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is clinical suspicion of CNS involvement by leukemia during screening.
Participants with treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: * Evaluable or measurable disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed * No evidence of significant vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study * Screening CNS radiographic study >/=4 weeks since completion of radiotherapy or surgical resection and >/=2 weeks since discontinuation of corticosteroids
Patients with primary CNS tumors and leptomeningeal disease are ineligible.
Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing.