Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of
      cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem
      cells. Also, imatinib mesylate may stop the growth of cancer cells by blocking the enzymes
      needed for cancer cell growth. Interferon alfa may interfere with the growth of cancer cells
      and slow the growth of cancer. When the healthy stem cells from a donor are infused into the
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood
      cells, and platelets. It is not yet known which treatment regimen is most effective in
      treating chronic phase chronic myelogenous leukemia.

      PURPOSE: This randomized phase III trial is studying imatinib mesylate with or without
      interferon alfa or cytarabine to see how well it works compared with interferon alfa followed
      by donor stem cell transplant in treating patients with newly diagnosed chronic phase chronic
      myelogenous leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the hematologic, cytogenetic, and molecular response rates in patients with
           newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib
           mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa
           standard therapy.

        -  Compare the group-dependent, progression-free and overall survival and time to
           progression in patients treated with these regimens.

        -  Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based
           therapy in patients eligible for transplantation.

        -  Compare the efficacy of reduced-intensity conditioning vs standard conditioning in
           patients over 45 years of age.

        -  Determine the time to and duration of hematologic, cytogenetic, and molecular responses
           and correlate these factors in patients treated with these regimens.

        -  Compare the short- and long-term adverse effects of these regimens in these patients.

        -  Compare the presentation, duration, and responses to therapy of accelerated and blastic
           phases in patients treated with these regimens.

        -  Determine the survival of high-risk patients after early allografting.

        -  Determine the influence of pre-transplantation therapies on the outcome of allogeneic
           stem cell transplantation in these patients.

      OUTLINE: This is a randomized, multicenter, pilot study. Patients are stratified according to
      participating center. Patients with low- to intermediate-risk disease are randomized to 1 of
      4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms
      with imatinib mesylate-based regimens.

        -  Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the
           absence of disease progression or unacceptable toxicity.

        -  Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive
           interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the
           start of imatinib mesylate.

        -  Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive
           cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the
           start of imatinib mesylate.

        -  Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa
           SC daily with or without hydroxyurea. In the absence of a complete response after 3
           months, patients may also receive low-dose cytarabine SC once daily. Treatment continues
           for up to 21 months.

      Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.

      Patients who fail therapy with imatinib mesylate and are eligible for an allogeneic
      transplantation are stratified according to availability of donor (HLA-identical related vs
      unrelated), status, and participating center. Patients are randomized to receive an
      allogeneic transplantation or continue any salvage therapy.

      Patients who are not eligible for allogeneic transplantation receive hydroxyurea and
      cytarabine or high-dose chemotherapy with autologous stem cell rescue followed by interferon-
      or imatinib mesylate-based therapy.

      Patients over 45 years of age are further randomized to receive an age-adjusted standard
      conditioning regimen or reduced intensity preparative regimen (mini transplantation) prior to
      allogeneic transplantation.

      Patients are followed every 6 months for 3 years and then annually thereafter.

      PROJECTED ACCRUAL: A total of 1,600 patients (400 per treatment arm) will be accrued for this
      study within 4-5 years.
    

Intervention name(s): recombinant interferon alfa; cytarabine; hydroxyurea; imatinib mesylate; allogeneic bone marrow transplantation; autologous bone marrow transplantation; peripheral blood stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Procedure; Procedure
Intervention MeSH terms: Interferons; Cytarabine; Interferon-alpha; Imatinib Mesylate; Hydroxyurea
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive