Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining more than one drug may kill more tumor cells. It is not
      yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic
      leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.

      PURPOSE: This randomized phase III trial is studying two different chemotherapy regimens and
      comparing them to see how well they work in treating adults with acute lymphoblastic
      leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the incidence of complete remission (CR) following induction with the ALL-2
           regimen (cytarabine and high-dose mitoxantrone) vs the L-20 regimen (vincristine and
           prednisone) in previously untreated adult patients with acute lymphoblastic leukemia
           (ALL), lymphoblastic lymphoma, and lymphoid blast crisis chronic myelogenous leukemia.

        -  Compare the time to CR, length of hospital stay, efficacy of treatment in Philadelphia
           chromosome-positive ALL, and the proportion of patients achieving durable (greater than
           5 years) remission in each treatment regimen.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      participating institution and antecedent lymphoid blast crisis of chronic myelogenous
      leukemia (yes vs no). Patients are randomized to one of two treatment arms.

      Arm I:

        -  Patients receive induction therapy consisting of cytarabine IV over 3 hours on days 1-5
           with high-dose mitoxantrone IV on day 3 and methotrexate intrathecally on days 2 and 4.
           Patients receive sargramostim (GM-CSF) subcutaneously or IV over 4 hours beginning on
           day 7 and continuing until blood counts recover.

        -  At 7-14 days following induction therapy, patients receive consolidation therapy
           consisting of vincristine IV on days 1, 8, 15, 22, and 29, oral prednisone 2-3 times
           daily on days 1-30 and methotrexate intrathecally on days 8, 15, 22, and 29.

        -  At 2-3 weeks following the last dose of vincristine, patients receive an additional
           course of consolidation therapy consisting of cyclophosphamide IV on day 1 and GM-CSF
           subcutaneously beginning on day 3 and continuing until blood counts recover.

        -  At 3-4 weeks following the second consolidation course, patients receive a third course
           of consolidation therapy consisting of cytarabine IV bolus on day 1 followed by
           continuous infusion cytarabine on days 1-4 with etoposide IV over 1 hour on days 1-3 and
           methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously
           beginning on day 6 and continuing until blood counts recover.

        -  Following recovery from the third consolidation course, patients receive a fourth
           consolidation course consisting of pegaspargase IV or intramuscularly (IM) on day 1.

        -  Following recovery from consolidation therapy patients receive 2 sequences of
           maintenance therapy with sequence one consisting of vincristine IV on days 1 and 8, oral
           prednisone 2-3 times daily on days 1-8, doxorubicin IV on day 15, oral mercaptopurine
           2-3 times daily on days 36-64, oral methotrexate on days 39, 46, 53, and 60,
           dactinomycin IV on day 85, and methotrexate intrathecally on days 36 and 43.

        -  At 2 weeks following sequence one of maintenance therapy, patients receive sequence two
           consisting of the same regimen as in the first sequence with the addition of
           cyclophosphamide IV and carmustine IV on day 15.

        -  Patients with CNS involvement receive whole brain radiotherapy in addition to
           chemotherapy regimens.

      Arm II:

        -  Patients receive induction therapy consisting of vincristine IV on days 1, 8, 15, 22,
           and 29, oral prednisone 2-3 times daily on days 1-29, cyclophosphamide IV on day 5,
           doxorubicin IV on days 23-25 and 42, methotrexate intrathecally on days 3, 5, 13, 16,
           32, and 34 and GM-CSF subcutaneously or IV over 4 hours beginning from days 7 and 27 and
           continuing until blood counts recover.

        -  At approximately 3 weeks following induction therapy, patients receive consolidation
           therapy consisting of cytarabine IV bolus on day 1 followed by continuous infusion
           cytarabine on days 1-5, with daunorubicin IV on days 1-3 and methotrexate intrathecally
           on days 2 and 4. Patients receive GM-CSF subcutaneously beginning on day 7 and
           continuing until blood counts recover.

        -  At 6-8 weeks following the first course of consolidation therapy, patients receive a
           second consolidation course consisting of cytarabine IV bolus on day 1 followed by
           continuous infusion cytarabine on days 1-4 with methotrexate IV on days 1-4 and
           methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously
           beginning on day 6 and continuing until blood counts recover.

        -  At 6-8 weeks following the second course of consolidation therapy, patients receive a
           third consolidation course consisting of pegaspargase IV or IM on day 1.

        -  At 3-4 weeks following the third course of consolidation therapy, patients receive a
           fourth consolidation course consisting of cyclophosphamide IV on day 1.

        -  At 3 weeks following the completion of consolidation therapy, patients receive the same
           maintenance regimen as in Arm I.

      Treatment continues in patients achieving complete response. Patients in both arms receive
      alternating sequences of maintenance therapy over 2 years.
    

Intervention name(s): dactinomycin; sargramostim; carmustine; cyclophosphamide; cytarabine; daunorubicin hydrochloride; doxorubicin hydrochloride; etoposide; mercaptopurine; methotrexate; mitoxantrone hydrochloride; pegaspargase; prednisone; vincristine sulfate; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Radiation
Intervention MeSH terms: Cytarabine; Dactinomycin; Prednisone; Cyclophosphamide; Carmustine; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Daunorubicin; Mitoxantrone; Mercaptopurine; Pegaspargase; Sargramostim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: blastic phase chronic myelogenous leukemia; untreated adult acute lymphoblastic leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; T-cell adult acute lymphoblastic leukemia; B-cell adult acute lymphoblastic leukemia; stage I adult lymphoblastic lymphoma; stage II adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; contiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma