Azacitidine After Allo Blood And Marrow Transplantation (BMT) for Chronic Myelogenous Leukemia (CML)
Condition: Stem Cell Transplantation; Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: Fludarabine; Busulfan; Thymoglobulin; Azacitidine; Stem Cell Transplant
Intervention description: 40 mg/m^2 by vein over 60 minutes on Day -5 through Day -2.; Busulfan administered at the dose calculated to achieve an area under curve (AUC) of 4000 µMol-min + 12% based on the pharmacokinetic studies (days -5, -4, -3, and -2).; 2.5 mg/kg by vein over about 4-6 hours on Day -3 through Day -1.; Start cycles of 32 mg/m^2 daily as an injection under the skin once a day over 5 days in a row, starting about 5 weeks after the transplant. This may be repeated once a month for up to 4 months after the transplant.; Stem cell infusion on day 0 administered by vein after collected from donor.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Azacitidine; Busulfan; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic Myelogenous Leukemia; CML; Donor stem cell transplant; Allogeneic stem cell transplantation; Stem cell transplant; ATG; Antithymocyte globulin; Vidaza; Azacitidine; 5-Azacitidine; 5-Aza; 5-AZC; Ladakamycin; NSC-102816; allotx; Busulfan; Busulfex; Myleran; Fludarabine; Fludarabine Phosphate; Tacrolimus; Methotrexate; Azacitidine maintenance therapy; molecular remission; HLA compatible donor; Engraftment; Chimerism; Graft vs host disease; GVHD

Summary:

      The goal of this clinical research study is to learn if Vidaza (azacitidine) when given to
      patients with CML after an donor stem cell transplant will increase the likelihood of
      achieving a complete remission of CML.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with age <= 75 years with CML in first chronic phase, which has failed to
             achieve a cytogenetic or molecular complete remission or has progressed after imatinib
             treatment. Criteria for failure are the international consensus criteria (Appendix H).
             Patients intolerant to tyrosine kinase inhibitor therapy are also eligible.

          2. Patients with age <= 75 with CML in accelerated phase or blast crisis that have <= 15%
             blasts in the blood and bone marrow at study entry.

          3. Donor: HLA-compatible related (HLA-A, -B, -DRB1 matched or with one-antigen mismatch)
             or HLA-compatible unrelated (HLA-A, -B, -C and -DRB1 matched or with one-antigen
             mismatch).

          4. Age 18 to 75 years.

          5. Zubrod performance status <= 2.

          6. Left ventricular ejection fraction => 40%.

          7. Pulmonary function test within the following parameters: forced expiratory volume at
             one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for
             carbon monoxide (DLCO) => 50% of expected, corrected for hemoglobin.

          8. Serum creatinine < 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min.

          9. Serum direct bilirubin < 1.5 mg/dL (unless Gilbert's syndrome)

         10. Serum glutamate pyruvate transaminase (SGPT) <= 200 IU/L unless related to patient's
             malignancy.

         11. Patients treated with any tyrosine kinase inhibitor, interferon or any experimental
             therapy are eligible.

         12. Patients with age <75 years with CML in second or subsequent chronic phase.

        Exclusion Criteria:

          1. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven
             days of therapy.

          2. Pleural/pericardial effusion or ascites estimated to be >1L.

          3. HIV-positive.

          4. Breast feeding or pregnancy. Pregnancy means a positive beta human chorionic
             gonadotropin (HCG) test in a woman with child bearing potential defined as not
             post-menopausal for 12 months or no previous surgical sterilization.

          5. Known or suspected hypersensitivity to azacitidine or mannitol.

          6. Patients with advanced malignant hepatic tumors.