Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients
Condition: Leukemia
MeSH terms: Leukemia
Intervention: Imatinib Mesylate; Fludarabine (Fludara); Busulfan; Antithymocyte Globulin (ATG); Tacrolimus; Methotrexate; Donor lymphocyte infusion (DLI); Stem Cell Transplant
Intervention description: 400 mg by mouth twice daily for 9 Days; 40 mg/m^2 by vein daily for 4 Days; 130 mg/m^2 by vein daily for 2 Days; 2.5 mg/kg by vein daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180.; 5 mg/m2 on days 1, 3, 6 and 11.; Infusion of lymphocytes from the original bone marrow donor by vein if relapse after >4 weeks of imatinib.; Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
Intervention MeSH terms: Vidarabine; Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Imatinib Mesylate; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Chronic Myelogenous Leukemia; Allogeneic Stem Cell Transplantation; Leukemia; Imatinib Mesylate; Gleevec; Busulfan; Busulfex; Myleran; Fludarabine; ATG; STI571; Antithymocyte Globulin; Thymoglobulin

Summary:

      Primary Objective:

      To estimate the probability of molecular complete remission at one year for the described
      sequential treatment approach, with nonablative hematopoietic transplantation, post
      transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive
      Chronic Myelogenous Leukemia (CML) not in blastic transformation.

      Secondary Objective:

      Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual
      disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib
      mesylate therapy, as well as engraftment, toxicity, disease free survival and survival,
      effect of busulfan pharmacokinetics on study outcome.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Ph+ chronic myelogenous leukemia (CML) in first chronic phase without a
             complete hematologic response after 3 months of Imatinib mesylate therapy, or >=35%
             Ph+ cells despite > 6 months of Imatinib mesylate treatment, or after disease
             progression from a complete or partial response. Any patient with accelerated phase or
             blast crisis who achieves a subsequent chronic phase is eligible. Patients must have
             an HLA matched related or unrelated donor or one antigen mismatched related donor.

          2. Patients should be less than 70 years of age. Patients less than 30 years of age who
             achieve a hematologic remission with imatinib therapy are eligible regardless of
             cytogenetic response.

          3. Patients are stratified as Group 1: First chronic phase, Group 2 Accelerated phase or
             blast crisis that achieved a hematologic remission with imatinib mesylate-based
             treatment.

        Exclusion Criteria:

          1. Zubrod Performance Scale (PS) >=2, uncontrolled infection, Creatinine > 2.0 mg/dl;
             Ejection fraction < 40%; Carbon Monoxide Diffusing Capacity (DLCO) < 45% of predicted;
             Serum bilirubin > 2 gm/dl; GPT (Glutamic-pyruvic transaminase) or GOT
             (glutamic-oxaloacetic transaminase)> 3 times normal values. Patients should not be
             human immunodeficiency virus (HIV) seropositive or pregnant.

          2. Patients should not have progressed to accelerated phase or blast crisis while
             receiving imatinib mesylate containing therapy.