Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Condition: Adult Acute Lymphoblastic Leukemia in Remission
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well giving imatinib mesylate together with chemotherapy and
      peripheral stem cell transplantation works in treating patients with newly diagnosed acute
      lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells
      from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer
      cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate
      together with chemotherapy and peripheral stem cell transplantation may be an effective
      treatment for acute lymphoblastic leukemia.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival
      (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).

      II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a
      BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following
      sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.

      III. Determine the feasibility of collecting adequate peripheral blood stem cells for
      autologous transplantation following imatinib mesylate (Gleevec) therapy.

      IV. Study the safety and efficacy of autologous peripheral stem cell transplantation
      following therapy with imatinib mesylate (Gleevec).

      V. Study the safety and efficacy of allogeneic stem cell transplantation following therapy
      with imatinib mesylate (Gleevec).

      VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after
      allogeneic or autologous stem cell transplant.

      OUTLINE:

      COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on
      a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to
      enrollment.

      COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on
      days 1-28.

      COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive
      methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and
      vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9,
      and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6
      hours on days 3, 4, 10, 11, 17, and 18.

      COURSE IV (imatinib mesylate): After blood counts recover after completion of course III,
      patients receive imatinib mesylate as in course II.

      COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT),
      autologous PBSCT, or no PBSCT.

      COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen [HLA]-matched sibling
      donor): Beginning 3-10 days after completion of course IV, patients with an HLA-matched
      sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients
      receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients
      then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to
      56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56)
      followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and
      filgrastim subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

      COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10
      days after completion of course IV, patients without an HLA-matched sibling donor receive
      etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive
      filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients
      receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and
      continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to
      -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours
      on day -2. Patients undergo PBSCT on day 0. Patients receive filgrastim SC beginning on day 0
      and continuing until blood counts recover.

      COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning 3-10
      days after completion of course IV, patients who are not candidates for PBSCT receive
      etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive
      filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts
      recover.

      COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post
      transplantation or on day 30 if no transplantation received and continuing for at least 1
      year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain
      reaction assays at least 3 months apart or until relapse.

      After completion of study treatment, patients are followed up monthly for 1 year, every 3
      months for 2 years, every 6 months for 2 years, then yearly for 5 years.
    

Intervention name(s): imatinib mesylate; methotrexate; vincristine sulfate; leucovorin calcium; peripheral blood stem cell transplantation; autologous hematopoietic stem cell transplantation; allogeneic hematopoietic stem cell transplantation; total-body irradiation; tacrolimus; filgrastim; etoposide; cyclophosphamide; cytarabine; laboratory biomarker analysis
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure; Radiation; Drug; Biological; Drug; Drug; Drug; Other
Intervention description(s): Given PO; Given IT and IV; Given IV; Given IV and PO; Undergo PBSCT; Undergo autologous PBSCT; Undergo allogeneic PBSCT; Undergo TBI; Given IV or PO; Given SC; Given IV; Given IV; Given IV; Correlative studies
Other intervention name(s): CGP 57148; Gleevec; Glivec; amethopterin; Folex; methylaminopterin; Mexate; MTX; leurocristine sulfate; VCR; Vincasar PFS; CF; CFR; LV; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell; TBI; FK 506; Prograf; G-CSF; Neupogen; EPEG; VP-16; VP-16-213; CPM; CTX; Cytoxan; Endoxan; Endoxana; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside
Intervention MeSH terms: Leucovorin; Cytarabine; Cyclophosphamide; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Imatinib Mesylate; Tacrolimus; Levoleucovorin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment