Clofarabine Plus Low-Dose Cytarabine for Patients With Higher-Risk Myelodysplastic Syndrome (MDS)
Condition: Leukemia; Myeloproliferative Diseases
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: Clofarabine; Cytarabine
Intervention description: Induction:
10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5)
Consolidation:
10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3); Induction:
20 mg subcutaneously twice daily for 7 days (days 1-7)
Consolidation:
20 mg subcutaneously twice daily for 5 days (days 1-5)
Intervention MeSH terms: Cytarabine; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myeloproliferative Diseases; Myelodysplastic Syndrome; (MDS); Relapsing; Refractory; Clofarabine; Clofarex; Clolar; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride

Summary:

      The goal of this clinical research study is to learn if clofarabine when given in combination
      with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could
      not be controlled with standard therapy. The safety of this treatment will also be studied.

      Clofarabine is designed to interfere with the growth and development of cancer cells.

      Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer
      cells and stop the DNA from repairing itself.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >/= 18 years.

          2. Diagnosis of MDS confirmed within 10 weeks prior to study entry according to World
             Health Organization (WHO) or French-American-British (FAB) criteria. Patients are
             either not eligible for or choose not to proceed with a stem cell transplant.

          3. MDS classified as follows: refractory anemia with excess blasts (RAEB-1) (5%-9% BM
             blasts); RAEB-2 (10%-19% BM Blasts); chronic myelomonocytic leukemia (CMML) (5%-19%
             Bone Marrow (BM) blasts); RAEB-t (20%-29% BM blasts) AND/OR by International Prostate
             Symptom Score (IPSS): intermediate-2 and high risk patients.

          4. No response, progression, or relapse (according to 2006 International Working Group
             (IWG) criteria; see section 8 for details) following at least 4 cycles of either
             azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were
             completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine,
             or SGI-110 defined as drug-related >/= grade 3 hepatic or renal toxicity leading to
             treatment discontinuation during the preceding 2 years.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.

          6. Willing to adhere to and comply with all prohibitions and restrictions specified in
             the protocol.

          7. Patient (or patient's legally authorized representative) must have signed an informed
             consent document indicating that the patient understands the purpose of and procedures
             required for the study and is willing to participate in the study.

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

          2. Active infection not adequately responding to appropriate antibiotics (i.e. ongoing
             temperatures of >/= 38 degree Celsius).

          3. Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease.
             Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of
             the bilirubin is indirect.

          4. Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the
             upper limit of normal.

          5. Serum creatinine > 1.5 mg/dL.

          6. Female patients who are pregnant or lactating.

          7. Patients with reproductive potential who are unwilling to following contraception
             requirements (including condom use for males with sexual partners, and for females:
             prescription oral contraceptives [birth control pills], contraceptive injections,
             intrauterine devices (IUD), double-barrier method [spermicidal jelly or foam with
             condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the
             study.

          8. Female patients with reproductive potential who do not have a negative urine or blood
             beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.

          9. Patients receiving any other concurrent investigational agent or chemotherapy,
             radiotherapy, or immunotherapy.

         10. No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of
             leukocytosis or use of hematopoietic growth factors (eg, G-CSF, Granulocyte-macrophage
             colony-stimulating factor (GM-CSF), procrit, aranesp, thrombopoietins) is allowed at
             any time prior to or during study if considered to be in the best interest of the
             patient.

         11. Psychiatric illness or social situation that would limit the patient's ability to
             comply with study requirements.