Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
Condition: T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin Hydrochloride; Dexamethasone; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Leucovorin Calcium; Mercaptopurine; Methotrexate; Nelarabine; Pegaspargase; Prednisone; Radiation Therapy; Thioguanine; Vincristine Sulfate
Intervention description: Given IM or IV; Given IV; Given IT, IV, or SC; Given IV; Given IV or PO; Given IV; Correlative studies; Given PO; Given PO; Given IT or PO; Given IV; Given IM or IV; Given IV or PO; Some patients undergo testicular and/or prophylactic cranial RT; Given PO; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; 6-methoxypurine arabinoside; Dexamethasone; Dexamethasone acetate; Prednisone; Cortisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Pegaspargase; Thioguanine; BB 1101; Calcium; 2-Aminopurine; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1895.0
Sex: All
Minimum age: 1 Year
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying different combination chemotherapy regimens and
      their side effects and comparing how well they work in treating young patients with newly
      diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in
      chemotherapy work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy)
      may kill more cancer cells. It is not yet known which combination chemotherapy regimen is
      more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic
      lymphoma. After a common induction therapy, patients were risk assigned and eligible for one
      or both post-induction randomizations: Escalating dose Methotrexate versus High Dose
      Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation
      therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low
      Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at
      diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction
      therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were
      all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High
      Risk and induction failures. Standard risk patients did not receive nelarabine, High risk
      T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures
      were assigned to receive Nelarabine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on
             AALL0434

          -  Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL)
             stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a
             diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or
             evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and
             express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7,
             CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional
             markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99
             will be assessed for expression; cases with uncertain expression will receive
             additional review within the appropriate Children's Oncology Group (COG) reference
             laboratory

          -  T-NHL PATIENTS:

               -  For T-NHL patients with tissue available for flow cytometry, the criterion for
                  diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e.
                  paraffin blocks), the methodology and criteria for immunophenotypic analysis to
                  establish the diagnosis of T-NHL defined by the submitting institution will be
                  accepted

          -  Prior therapy restrictions

               -  Patients shall have had no prior cytotoxic chemotherapy with the exception of
                  steroids and/or IT cytarabine

               -  IT chemotherapy with cytarabine is allowed prior to registration for patient
                  convenience; this is usually done at the time of the diagnostic bone marrow or
                  venous line placement to avoid a second lumbar puncture; (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); systemic
                  chemotherapy must begin within 72 hours of this IT therapy

               -  Patients diagnosed as having T-NHL or T-ALL with respiratory distress or
                  hyperleukocytosis may require steroids prior to the initiation of additional
                  systemic therapy; they are eligible for AALL0434 and will be stratified, based on
                  the initial complete blood count (CBC); steroid pretreatment may alter the risk
                  group assessment; if the T-ALL patient's clinical status precludes a lumbar
                  puncture within 48 hours of the initiation of steroid therapy, T-ALL patients
                  CANNOT be classified as low risk and will be Intermediate or high risk based on
                  the results of the day 29 marrow as above; patients with T-NHL who receive
                  steroid pre-treatment will be classified as high risk; the dose and duration of
                  previous steroid therapy should be carefully documented

               -  For the management of airway compromise, patients who have received emergent
                  chest irradiation up to 600 cGy will be eligible for this study

          -  Patients with a prior seizure disorder requiring anti-convulsant therapy are not
             eligible to receive nelarabine; in addition, patients with pre-existing grade 2 (or
             greater) peripheral neurotoxicity, as determined prior to Induction treatment by the
             treating physician or a neurologist, are not eligible to receive nelarabine; these
             restrictions in eligibility are designed to prevent excessive nelarabine-induced
             central and peripheral neurotoxicity in at-risk patients; for the purposes of this
             study, this includes any patient that has received anticonvulsant therapy to
             prevent/treat seizures in the prior two years

        Exclusion Criteria:

          -  Pregnant or lactating females are ineligible

          -  Patients with Down syndrome are ineligible to enroll onto this study

          -  For T-NHL patients the following additional exclusion criteria apply:

               -  B-precursor lymphoblastic lymphoma

               -  Morphologically unclassifiable lymphoma

               -  Absence of both B-cell and T-cell phenotype markers in a case submitted as
                  lymphoblastic lymphoma

               -  CNS3-positive or testicular involvement