Study of Clofarabine in Combination With Low Dose Cytarabine to Treat Myelodysplastic Syndromes

Study Overview
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Brief Summary
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This is an interventional, multicenter, open label, phase II study designed to evaluate the safety and efficacy of Clofarabine in combination with low dose Cytarabine in untreated patients with poor risk of Myelodisplastic Syndromes.

Official Title
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Phase II Study of Clofarabine in Combination With Low Dose Cytarabine for Untreated Patients With Poor Risk Myelodysplastic Syndromes

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Clofarabine plus low dose Ara-C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients age 55 to 80 years Written informed consent to participate in the clinical trial Morphologically confirmed diagnosis of MDS according to WHO classification, and IPSS INT-2 or high risk according to IPSS index ECOG performance status 0-2 No previous chemotherapy Serum bilirubin ≤1.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction) AST and ALT ≤2.5 times ULN Alkaline phosphatase ≤2.5 times ULN Serum creatinine ≤ 1 mg/dl: if serum creatinine > 1.0 mg/dl, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine) -1.154 x age in years -0-023 x 0.742 (if patient is female) x 1.212 (if patient is black) HIV negative Exclusion Criteria: Have had any other chemotherapy or any investigational therapy as a treatment for MDS. Patients who received chemotherapy for other cancers than MDS/AML can be enrolled, provided that at least 6 months elapsed from accomplishment of the last course of chemo. Have had a prior hematopoietic stem cell transplant for MDS Have an uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). Have a psychiatric disorder that would interfere with consent, study participation, or follow-up. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart Have had any prior treatment with Clofarabine Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions: 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. Have prior positive test for the Human Immunodeficiency Virus (HIV), HCV, HBV.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Clofarabine combined with low dose Ara-C | Drug: Clofarabine plus low dose Ara-C<br>* Clofarabine 10 mg/m2 by a 1-hr i.v infusion, once daily, from day 1 to 5. Ara-C 10 mg/m2, subcutaneously, twice a day (q12 hrs), from day 1 to 15. Clofarabine will be given 4 hours before the 2nd dose of Ara-C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the remission rate according to the combination regimen |  | 19 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response and survival |  | 19 months | 
| Time to transformation in AML |  | 19 months | 
| To determine the relationship of cytogenetic abnormalities and response to treatment |  | 19 months | 
| To determine the safety and tolerability of the combination regimen |  | 19 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Clofarabine, Low Dose Cytarabine, Poor risk MDS