Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Syndrome
Intervention: Clofarabine; Busulfan; Fludarabine; Stem Cell Infusion; Thymoglobulin (ATG); Filgrastim
Intervention description: Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily.
Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC)); Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.; Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Busulfan; Clofarabine; Thymoglobulin; Antilymphocyte Serum; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia; AML; Myelodysplastic Syndrome; MDS; Chronic Myeloid Leukemia; CML; Busulfan; Busulfex; Myleran; Fludarabine; Fludara; Fludarabine Phosphate; Clofarabine; Clofarex; Clolar; Allogeneic stem cell transplantation; ASCT; Stem Cell; Gleevec; Imatinib Mesylate

Summary:

      The goal of this clinical research study is to find the best dose of clofarabine and
      fludarabine that can be given with busulfan followed by an allogeneic blood stem cell
      transplant. Researchers will study whether this combination can help to control the disease,
      and look at the safety of this combination. Researchers also want to find out if combining
      busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine
      will improve the treatment, compared with the previous standard method using busulfan and
      fludarabine alone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent
             relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high
             risk International Prognostic Scoring System score (IPSS scores) (16), and having
             failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome
             positive and having failed / being resistant to therapy based on Gleevec or other
             tyrosine kinase inhibitors.

          2. Patient has not been administered intensive systemic chemotherapeutic drugs within 21
             days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec,
             alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose
             cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All
             tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at
             least one week prior to admission for this treatment.

          3. No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter
             if there is uncertainty regarding whether a previous infection is resolved on
             appropriate antibiotics therapy.

          4. age </= 60

          5. A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or
             DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor,
             matched with molecular high-resolution technique per current standard for the BMT
             program).

          6. ZUBROD performance status <2

          7. Life expectancy is not severely limited by concomitant illness.

          8. Left ventricular ejection fraction >/=45% No uncontrolled arrhythmias or symptomatic
             cardiac disease.

          9. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon
             monoxide diffusing capacity (DLCO) >/= 50% of expected corrected for hemoglobin. In
             patients </= 7 years pulmonary function will be assessed per pediatric BMT routine

         10. Serum creatinine </= 1.5 mg%.

         11. Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml, serum bilirubin and alkaline
             phosphatase within accepted laboratory standard normal limits or considered not
             clinically significant. No evidence of chronic active hepatitis or cirrhosis. If
             positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror
             to determining study eligibility.

         12. Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy
             test in all women of child-bearing-potential in accordance with departmental routine).

         13. Patient or patient's legal representative, parent(s) or guardian able to sign informed
             consent.

        Exclusion Criteria:

          1. Effusion or ascites estimated to be >1L prior to drainage.

          2. HIV-positive.

          3. Hepatitis C or HBsAg positive

          4. Prior stem cell transplant after a myeloablative conditioning program (such as
             busulfan-based using a total dose of >/= 12 mg/kg given by mouth or >/= 10 mg/kg IV,
             or a total-body irradiation-based program.

          5. Active or prior Central Nervous System (CNS) leukemia

          6. Biphenotypic acute leukemia.