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

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  months (years) 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)

Subjects with known active or history of CNS involvement by malignancy

Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollment

Patients with asymptomatic CNS involvement are allowed.

CNS metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last  months prior to randomization.

Known CNS involvement at diagnosis

Clinical Evidence of CNS disease

Leptomeningeal disease as the only site of CNS involvement

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 , 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 , defined as presence of < /uL WBCs in CSF and cytospin positive for blasts, or > /uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS a: < /uL red blood cells (RBCs); < /uL WBCs and cytospin positive for blasts\r\n**** CNS b: >= /uL RBCs; < /uL WBCs and cytospin positive for blasts\r\n**** CNS c: >= /uL RBCs; >= /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 , defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs\r\n*** CNS , defined as presence of < /uL WBCs in CSF and cytospin positive for blasts, or > /uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS a: < /uL RBCs; < /uL WBCs and cytospin positive for blasts;\r\n**** CNS b: >= /uL RBCs; < /uL WBCs and cytospin positive for blasts;\r\n**** CNS c: >= /uL RBCs; >= /uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm

Subjects with radiologically-detected CNS lymphoma or CNS  disease (presence of >= /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

Active CNS involvement

EXCLUSION - TREATMENT: Central nervous system (CNS) abnormalities: presence of CNS- disease defined as detectable cerebrospinal blast cells in a sample of cerebrospinal fluid (CSF) with ?  white blood cells (WBCs) per mm^; 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 known involvement of the CNS by malignancy will be excluded.

Evidence of CNS involvement by NHL

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  months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imaging

Active CNS involvement of their malignancy.

Active CNS involvement by malignant cells (?  months from the conditioning)

CNS metastatic involvement

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

TREATMENT WITH SJCAR: CNS-/CNS- disease with neurologic changes

Active central nervous system (CNS) disease\r\n* Definition: any patient receiving active CNS therapy (defined as more than  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  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

Known clinically active CNS involvement.

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 , 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 , defined as presence of < /uL WBCs in CSF and cytospin positive for blasts, or > /uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n*** CNS a: < /uL red blood cells (RBCs); < /uL WBCs and cytospin positive for blasts\r\n*** CNS b: ? /uL RBCs; < /uL WBCs and cytospin positive for blasts\r\n*** CNS c: ? /uL RBCs; ? /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  disease (presence of ? /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)

History or clinical signs of meningeal or active CNS involvement

Oral hydroxyurea and/or one dose of cytarabine (up to  g/m^) 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 , 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  consecutive lumbar punctures (LPs) with no evidence of CNS leukemia, and must be clinically stable for at least  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- disease or CNS- disease with neurological changes

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

Subjects with CNS involvement may be included on the study as long as they have not had any seizure activity in past  weeks

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 , defined as absence of blasts in CSF on cytospin preparation, regardless of the number of white blood cells (WBCs);\r\n*** CNS , defined as presence of < /uL WBCs in CSF and cytospin positive for blasts, or > /uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS a: < /uL red blood cells (RBCs); < /uL WBCs and cytospin positive for blasts;\r\n**** CNS b: >= /uL RBCs; < /uL WBCs and cytospin positive for blasts;\r\n**** CNS c: >= /uL RBCs; >= /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

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  days after completion of radiation is required for confirmation of response

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  weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment

Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within  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

History or presence of non-malignant CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

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 CNS disease will be excluded from study entry; subjects with concurrent CNS disease and bone marrow relapse who have responded to CNS-directed therapy prior to enrollment/lymphodepletion will be allowed to participate; subjects with CNS disease and concurrent bone marrow relapse will be eligible; intrathecal chemotherapy will be allowed to continue between lymphodepleting chemotherapy and cell infusion

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

In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of -azacytidine and avelumab will be at least  days OR at least  half-lives for cytotoxic/noncytotoxic agents, whichever is longer; the toxicity from prior therapy should have resolved to grade =< , however alopecia and sensory neuropathy grade =<  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  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)

CNS involvement with malignancy.

Subjects with history of central nervous system (CNS) disease are allowed if at the time of day  of the study there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least  weeks prior to the first study drug administration in a subject with no clinical signs of CNS disease

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  weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment

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  days prior to trial treatment

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  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  months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging

For lymphodepletion chemotherapy, JCAR 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  months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging

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 >  weeks before enrollment

Subjects with signs or symptoms indicative of CNS involvement; a CNS evaluation should be performed as clinically appropriate to rule our CNS involvement

CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity

Relapsed/refractory leukemia in nd 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 ? % blasts in the bone marrow or must have definitive extramedullary disease (e.g. chloromas, skin lesions). Patients may have asymptomatic CNS  or CNS  disease, but not CNS  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  weeks prior to enrollment

Patients with central nervous system (CNS)  or CNS  disease are eligible; patients with isolated CNS relapse or CNS  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

History of CNS involvement by MM

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  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

Patients with active CNS disease

Active CNS disease as identified by positive CSF cytospin at time of enrollment

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 >  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 >  weeks before 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  weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment

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  month

At the time of enrollment, specified baseline CNS conditions must be =< grade II toxicity per Common Terminology Criteria for Adverse Events (CTCAE) . 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

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

Evidence for active CNS involvement by leukaemia

Patients with active CNS disease

History or clinical evidence of cnetral nervous system (CNS) HL

 Evidence of CNS involvement by NHL.

Patients with a history of ventral nervous system (CNS) myeloma or other CNS malignancy.

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

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 central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression)

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 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 , 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 , defined as presence of < /uL WBCs in CSF and cytospin positive for blasts, or > /uL WBCs but negative by Steinherz/Bleyer algorithm\r\n* CNS 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  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  or CNS  classification

Patients with active CNS leukemia involvement defined as CNS- by CSF findings only are eligible but will have their CTL infusion delayed until CNS disease is reduced to CNS- or CNS- by CSF findings. Patients with other forms of active CNS- 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- leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least  months prior to CTL infusion. Patients must have no acute/ongoing neurologic toxicity > Grade  with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past  months.

Active CNS involvement by malignancy, defined by CNS- per NCCN guidelines.

Patients with primary CNS tumor or CNS tumor involvement

Evidence of CNS involvement with DLBCL

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  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.

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 >=  drug-related CNS toxicity. Participants with signs or symptoms of CNS involvement should have a computed tomography (CT) or magnetic resonance imaging (MRI)

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 >  weeks before enrollment

Presence of CNS- disease and CNS- disease with neurological changes

CNS disease:

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  months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.

Patients with a history of central nervous system (CNS) leukemia are eligible if they are not symptomatic from current CNS involvement\r\n* If there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly

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 >  weeks before enrollment

Cohort : 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

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  weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment

Known active CNS involvement

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  weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment

No active CNS disease

Known or clinically suspected CNS involvement

Patients may have CNS ,  or  disease.

Patients may have CNS  or CNS  disease but not CNS .

CNS  (< /?L WBCs in CSF and cytospin negative for blasts)

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  weeks

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  weeks; and if the patient does not currently require steroids

Patients with uncontrolled CNS tumor metastatic involvement

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 CNS involvement unless they are at least  weeks from prior therapy completion.

History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

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

Patient with active CNS disease.

Patient must have relapsed/refractory acute myelogenous leukemia (AML) with ? % blast in the bone marrow or biopsy confirmed chloroma. Patient may have CNS ,  or  disease. Isolated CNS relapse is not eligible.

Known, clinically suspected, or history of CNS tumor involvement.

Clinical evidence of active CNS leukemic involvement

Patients has primary CNS tumor or CNS tumor involvement

Patients with CNS  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  weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement

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

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.

Primary CNS tumor or CNS tumor involvement

Presence of CNS involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical Monitor

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  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  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  weeks (cohort )

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

In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of ponatinib administration will be at least  weeks for cytotoxic agents OR at least  half-lives for cytotoxic/non-cytotoxic agents; use of one dose of cytarabine (up to  g/m^) 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  simultaneous cerebrospinal fluid (CSF) evaluations

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.