SWOG-9400 Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Previously Untreated Acute Lymphocytic Leukemia
Condition: Leukemia; Neutropenia; Thrombocytopenia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thrombocytopenia; Neutropenia
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining chemotherapy with bone marrow transplantation may
      allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

      PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with or
      without bone marrow transplantation in treating patients who have acute lymphocytic leukemia.
    

Detailed description: 
      OBJECTIVES: I. Evaluate if front line induction therapy with daunorubicin, vincristine,
      prednisone, and asparaginase is sufficiently effective to warrant a phase III trial in
      patients with acute lymphocytic leukemia (ALL). II. Assess the toxicity of this regimen in
      this patient population. III. Assess disease free and overall survival and toxicity
      associated with allogeneic bone marrow transplantation for ALL patients in first remission
      following induction and consolidation therapy. IV. Assess disease free and overall survival
      and toxicity associated with sequential regimens of mercaptopurine, methotrexate and
      vincristine, doxorubicin, dexamethasone, and cyclophosphamide, thioguanine, and cytarabine in
      ALL patients in first remission who are ineligible for allogeneic bone marrow
      transplantation. V. Evaluate the prognostic significance of cell surface immunophenotype,
      Philadelphia chromosome, and polymerase chain reaction detected BCR/abl fusion in this
      patient population.

      OUTLINE: Patients are stratified according to age (15 to 29 vs 30 to 49 vs 50 to 65),
      performance status (0-1 vs 2-3), participating center, and candidate for allogeneic bone
      marrow transplantation (yes vs no). Patients receive induction chemotherapy consisting of
      daunorubicin IV on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days
      1-28, and asparaginase IV or intramuscularly (IM) on days 15-24. Patients with persistent
      leukemia on day 21, receive additional induction therapy consisting of daunorubicin IV on
      days 22 and 23, vincristine IV on days 29 and 36, and oral prednisone continuing to day 42.
      Patients with CNS leukemia receive additional therapy beginning on day 1 of induction
      chemotherapy consisting of methotrexate intrathecally (IT) or intraventricularly twice weekly
      until blasts are absent in spinal fluid. Patients receive oral leucovorin calcium every 6
      hours for a total of 4 doses following each IT dose in the absence of blood count recovery.
      Following absence of spinal fluid blasts, patients receive methotrexate IT or
      intraventricularly weekly for 4 weeks then monthly for 1 year. Patients also receive cranial
      radiotherapy during consolidation therapy 5 days a week for 2.5 weeks. Patients with A1 bone
      marrow receive consolidation therapy following completion of induction therapy and blood
      count recovery. Patients receive consolidation therapy consisting of cyclophosphamide IV on
      days 1, 15, and 29, cytarabine IV on days 2-5, 9-12, 16-19, and 23-26, oral mercaptopurine on
      days 1-28, and methotrexate IT on days 2, 9, 16, and 23. Following completion of
      consolidation therapy, patients eligible for allogeneic bone marrow transplantation receive
      total body radiotherapy 3 times a day on days -7, -6, -5, and twice on day -4, and eptoposide
      IV over 4 hours on day -3. Patients undergo allogeneic bone marrow transplantation on day 0.
      Following completion of consolidation therapy, patients ineligible for allogeneic bone marrow
      transplantation receive maintenance therapy consisting of oral mercaptopurine on days 1-63,
      and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients receive
      subsequent courses of maintenance therapy when blood counts recover. Patients receive a
      second course of maintenance therapy consisting of vincristine IV on days 1, 8, 15, and 22,
      doxorubicin IV on days 1, 8, 15, and 22, and oral dexamethasone on days 1-28. Patients
      receive a third course consisting of cyclophosphamide IV on day 1, oral thioguanine on days
      1-14, and cytarabine IV on days 3-6 and 10-13. Patients receive a fourth course consisting of
      oral mercaptopurine and oral methotrexate daily for 2 years. Patients are followed monthly
      for 6 months and then every 2 months thereafter.

      PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study.
    

Intervention name(s): asparaginase; cyclophosphamide; cytarabine; daunorubicin hydrochloride; dexamethasone; doxorubicin hydrochloride; etoposide; leucovorin calcium; mercaptopurine; methotrexate; prednisone; thioguanine; vincristine sulfate; allogeneic bone marrow transplantation; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): 10,000 units/d IV or IM 15 - 24; con: 650 mg/m2 IV 1, 15, 29 maint: 650 mg/m2 IV 1; cons: 75 mg/m2/d IV Push 2 - 5, 9 - 12, 6 - 19, 23 - 26; ind: 60 mg/m2 IV 22 and 23; main: 10 mg/m2/day PO 1 - 28; main: 25 mg/m2 IV 1, 8, 15, and 22; 60 mg/kg based on ideal body weight day -3; 5 mg q 6 hours for 4 doses, PO 1, 3, 8, 11 after each methotrexate if WBC < 3,000 /μl; con: 60 mg/m2 PO 1 - 28; 10 mg/m2 IT or IV, d 2, 9, 16, and 23; Maximum 15 mg/admin; ind: 60 mg/m2/d PO 1 - 21*, 22 - 28 Patients will receive full dose through day 8 and then tapered to zero between Day 29 and 42.
ind2: 60 mg/m2/d PO through day 42; main: 60 mg/m2/day PO 1 - 14; ind: 1.4 mg/m2 2 mg max, IV 1, 8, 15, and 22 ind2: 1.4 mg/m2 2 mg max IV 29 and 36 main: 1.5 mg/m2 2 mg max, IV 1, 8, 15, and 22; day 0; day -7 through day -4 total dose of radiation is 1,320 cGy.
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Prednisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine; Levoleucovorin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated adult acute lymphoblastic leukemia; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia; L3 adult acute lymphoblastic leukemia; neutropenia; thrombocytopenia