Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML)
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Myelodysplastic Syndromes; Syndrome
Intervention: Clofarabine 40mg/m^2; Idarubicin 10mg/m^2; Ara-C 0.75 g/m^2; Clofarabine 22.5mg/m^2; Ara-C 1 g/m^2; Idarubicin 6 mg/m^2
Intervention description: 40 mg/m^2 by vein over 1 hour daily for 5 days.; 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Clofarabine + Idarubicin plus Ara-C:
6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.; 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.; 22.5 mg/m^2 by vein over 1 hour daily for 5 days.; 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.; 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Intervention MeSH terms: Cytarabine; Clofarabine; Idarubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: No
Keywords: Chronic Myeloid Leukemia; CML Myeloid Blast Phase; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Clofarabine; Clofarex; Clolar; Ara-C; Cytarabine; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Idarubicin; Idamycin

Summary:

      The goal is to compare the drug combinations clofarabine/idarubicin/ara-C, clofarabine/ara-C,
      and clofarabine/idarubicin in the treatment of patients with Acute Myeloid Leukemia,
      high-grade MDS, or myeloid blast phase of Chronic Myeloid Leukemia who have relapsed
      following their initial therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >/= 18 years and < 60 years.

          2. Must be in first relapse of AML, or must receive treatment as first salvage in primary
             refractory AML; or have high-risk MDS (>/= 10% blasts) with not more than one prior
             regimen of chemotherapy (therapy with hematopoietic growth factors, biological or
             targeted therapies are not counted). Patients in CML myeloid blast phase may receive
             clofarabine as frontline therapy or in first salvage.

          3. Total bilirubin </= 2mg/dL, Serum glutamic pyruvic transaminase (SGPT) </= 4 upper
             limit of normal (ULN), creatinine </= 2.0mg/dL.

          4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          5. Signed informed consent.

          6. Male and female patients who are fertile agree to use an effective barrier method of
             birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
             Female patients need a negative serum or urine pregnancy test within 7 days of study
             enrollment (applies only if patient is of childbearing potential. Non-childbearing is
             defined as >= 1 year postmenopausal or surgically sterilized).

        Exclusion Criteria:

          1. Previous treatment with clofarabine.

          2. Active, uncontrolled, systemic infection considered opportunistic, life threatening,
             or clinically significant at the time of treatment, or any severe, concurrent disease,
             which, in the judgment of the investigator and after discussion with the Principal
             Investigator, would make the patient inappropriate for study entry.

          3. Symptomatic central nervous system (CNS) involvement.

          4. Patients who receive other chemotherapy. Patients must have been off previous therapy
             of >/= 2 weeks and must have recovered from acute toxicity of all previous therapy
             prior to enrollment. Treatment may start earlier following discussion with the
             Principal Investigator.

          5. Cardiac ejection fraction </= 30%.