Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS)
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Decitabine; Clofarabine
Intervention description: Decitabine 20 mg/m^2 by vein daily over 1-2 hours for 5 days for both Group 1 and Group 2. Group 1 receives decitabine on Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21; and Group 2 is on Days 1-5 of every cycle.; Clofarabine 10 mg/m^2 by vein daily over 1-2 hours for 5 days on Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24.
Intervention MeSH terms: Decitabine; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelodysplastic Syndrome; MDS; Leukemia; Decitabine; clofarabine; Dacogen®; Clolar®

Summary:

      The goal of this clinical research study is to learn if sequential administration of
      decitabine and clofarabine can help to control MDS better than decitabine alone. The safety
      of this drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with higher risk MDS (IPSS int-2 or high, or >/= 10% blasts as defined by WHO
             or FAB). - No prior intensive chemotherapy or high-dose cytarabine (>/= 1 g/m2). -
             Prior biologic therapies (</= 1 cycle of prior decitabine or azacitidine), targeted
             therapies, or single agent chemotherapy is allowed. - Off chemotherapy for 2 weeks
             prior to entering this study with no toxic effects of that therapy, unless there is
             evidence of rapidly progressive disease. - Hydroxyurea is permitted for control of
             counts prior to treatment. - Hematopoietic growth factors are allowed. .

          2. Age >/= 18 years.

          3. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          4. Have adequate renal function (serum creatinine </= 1.5 mg/dL)

          5. Serum bilirubin </= 1.5 x upper limit of normal (ULN)

          6. Aspartate transaminase (AST) or alanine transaminase (ALT) </= 2.5 x ULN

          7. Alkaline phosphatase </= 2.5 x ULN

          8. Provide signed written informed consent.

          9. Capable of understanding the investigational nature, potential risks and benefits of
             the study, and able to provide valid informed consent.

         10. Female patients of childbearing potential must have a negative pregnancy test within 2
             weeks prior to enrollment.

         11. Male and female patients must use an effective contraceptive method during the study
             and for a minimum of 6 months after study treatment.

        Exclusion Criteria:

          1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
             specified in the protocol.

          2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
             before study entry with the exception of hydroxyurea. The patient must have recovered
             from all acute toxicities from any previous therapy.

          3. Have any other severe concurrent disease, or have a history of serious organ
             dysfunction or disease involving the heart, kidney, liver, or other organ system that
             may place the patient at undue risk to undergo treatment.

          4. Patients with a systemic fungal, bacterial, viral, or other infection not controlled
             (defined as exhibiting ongoing signs/symptoms related to the infection and without
             improvement, despite appropriate antibiotics or other treatment)

          5. Pregnant or lactating patients.

          6. Any significant concurrent disease, illness, or psychiatric disorder that would
             compromise patient safety or compliance, interfere with consent, study participation,
             follow up, or interpretation of study results

          7. Any concurrent malignancy (with the exception of exclusion # 8)

          8. Exceptions to inclusion # 7: a) Patients with treated non-melanoma skin cancer, in
             situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free
             duration, are eligible for this study if definitive treatment for the condition has
             been completed; b) Patients with organ-confined prostate cancer with no evidence of
             recurrent or progressive disease based on prostate-specific antigen (PSA) values are
             also eligible for this study if hormonal therapy has been initiated or a radical
             prostatectomy has been performed.