A randomized study of decitabine alternating with clofarabine versus decitabine until failure in patients with higher risk MDS
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.
Disease Group: Leukemia
Treatment Agent: Clofarabine
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: Patients may require hospitalizations of up to 5 days for clofarabine. ;Hospitalization is not mandatory and outpatient administration of chemothearpy ;is permitted.
Return Visit: Patients will return to MD Anderson Cancer Center prior to each course.
Home Care: Therapy will be administered either at MDACC or outside MDACC as allowed and ;approved by the principal investigator. Patients may be followed locally in ;between therapies for blood work and supportive care.
Primary objective: 1. To estimate the difference of the event-free survival rate between decitabine and clofarabine alternating with decitabine. Secondary objectives: 1. Complete remission (CR) at 3 months and 6 months 2. Partial response, hematologic improvement, and transfusion independence 3. Mortality after 1 cycle of clofarabine on arm A and after 3rd cycle of decitabine on arm B 4. Overall survival 5. Safety and toxicity 6. Rate and time to AML transformation
IRB Review and Approval Date: 01/28/2010
Recruitment Status: Not Accepting
Projected Accrual: 80
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) 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.
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.