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
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
Acute symptomatic CNS hemorrhage
Clinical Evidence of CNS disease
CNS lymphoma.
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)
Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded
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
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.
TREATMENT WITH SJCAR19: CNS-1/CNS-2 disease with neurologic changes
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
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)
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
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).
Presence of CNS-3 disease or CNS-2 disease with neurological changes
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
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.
History of primary CNS malignancy, or leptomeningeal disease or CNS metastases
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
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
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
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
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
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
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)
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
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
CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
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
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.
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
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
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
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
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
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
Active CNS disease as identified by positive CSF cytospin at time of enrollment
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 with active known CNS lymphoma. Patients with history of CNS leukemia now in remission are eligible for the trial.
At the time of enrollment, specified baseline CNS conditions must be =< grade II toxicity per Common Terminology Criteria for Adverse Events (CTCAE) 3.0 criteria; this includes the following conditions: arachnoiditis/meningismus/radiculitis, ataxia, CNS cerebrovascular ischemia, CNS necrosis/cystid progression, cognitive disturbance, confusion, dizziness, encephalopathy, hydrocephalus, leak - cerebrospinal fluid, leukoencephalopathy (radiologic findings), mental status, psychosis, seizure, somnolence/depressed level of consciousness
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
CNS or testicular leukemia at diagnosis allowed
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
Serious underlying medical condition or infection other than HIV that would contraindicate SC-EPOCH-R; examples include, but are not limited to:\r\n* Severe AIDS-related wasting\r\n* Severe intractable diarrhea\r\n* Active inadequately treated opportunistic infection of the central nervous system (CNS)\r\n* Primary CNS lymphoma
Primary CNS lymphoma
Patients with active CNS disease
History or clinical evidence of cnetral nervous system (CNS) HL
Patients with metastatic disease limited to the CNS
Patients with a history of ventral nervous system (CNS) myeloma or other CNS malignancy.
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
Known leptomeningeal disease or CNS midline shifts
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
Subject has symptomatic/untreated CNS disease
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 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
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
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)
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 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
CNS disease prophylaxis must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
CNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
Patients with CNS malignancies (primary or metastatic)
Known untreated or unstable CNS metastatic disease.
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
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
Current or history of CNS lymphoma
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.
History or evidence of CNS disease. Radiographic screening of all participants without history of CNS metastasis is required.
Active CNS lymphoma.
Presence of CNS-3 disease and CNS-2 disease with neurological changes
Patients must have previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
CNS disease:
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.
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).
Presence of symptomatic CNS lymphoma
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
Cohort 2: Participants must have progressive disease in CNS or non-CNS sites
Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesions
Symptomatic CNS disease
No active CNS disease
Patients may have CNS 1, 2 or 3 disease.
Patients may have CNS 1 or CNS 2 disease but not CNS 3.
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.
Patients with metastatic disease i.e. leptomeninges, multi-focal lesions in the CNS
CNS metastatic disease
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.
Patient with active CNS disease.
CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease
Patient must have relapsed/refractory acute myelogenous leukemia (AML) with ? 5% blast in the bone marrow or biopsy confirmed chloroma. Patient may have CNS 1, 2 or 3 disease. Isolated CNS relapse is not eligible.
Patients with CNS 3 disease or symptomatic CNS disease
Patients must have histological proof of a cancer - melanoma, breast, or lung cancer - which has spread to the CNS or glioblastoma (GBM) or other primary malignant neoplasm of the CNS which has been treated with standard treatments, which may include radiation, and must be measurable (RECIST).
Active ALL in the CNS or testes
Medically apparent CNS lymphoma or leptomeningeal disease
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
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
Symptomatic CNS disease
Primary or secondary CNS lymphoma
Known primary CNS lymphoma
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
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)
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
History of CNS hemorrhage within 28 days of study entry. This criterion may be waived at the investigator's request if the CNS hemorrhage was asymptomatic, with approval of the Medical Monitor
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 SCNSL actively receiving treatment for extra-CNS disease are 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