A Study of Oral Clofarabine in Adult Patients With Myelodysplastic Syndromes (MDS)

Study Overview
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Brief Summary
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This study will be used to determine the maximum tolerated dose of oral clofarabine when administered daily for 14 consecutive days repeated every 21 days.

Official Title
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A Phase I, Open-Label, Dose-Finding and Food Effect Study of Oral Clofarabine in Previously Treated Adult Patients With Myelodysplastic Syndromes (MDS)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: clofarabine
* Drug: clofarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed, written informed consent. Be at least 18 years old. Have a pathologically confirmed MDS and score according to the IPSS at study entry. Pathologic confirmation is the responsibility of the investigator. Have been treated previously for MDS as follow: a.Patients must have had at least 1, but no more than 2, prior treatment regimens; b.Patients must not have refractory (i.e., disease progression or no evidence of response while on treatment) to more than 1 prior treatment regimen. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Be able to comply with study procedures and follow-up examinations. Have adequate hepatic and renal function. Be non-fertile or agree to use birth control during the study through the end of the last treatment visit and at least 90 days after. Exclusion Criteria: Have had a readjustment of dose and/or schedule of erythropoietin, granulocyte colony stimulating factor(G-CSF) or other growth factors within 8 weeks prior to the first dose of oral clofarabine. Have had any other chemotherapy or any investigational therapy for MDS within 4 weeks of the first dose of oral clofarabine. Have not recovered to ≤ Grade 2 in severity of any drug-related non-hematologic toxicity prior to the first dose of oral clofarabine. Have an uncontrolled systemic fungal, bacterial, viral or other infection. Have a history of serious disease involving the heart. Have a clinically significant cardiac assessment at screening or a known family history QT prolongation. Currently uses a medication known to prolong the QT interval. Have had any prior treatment with clofarabine (IV or oral). Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years after completing curative intent therapy except for the following: 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 or 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). Have gastrointestinal disease or prior surgery, which may affect the ability of the patient to absorb oral clofarabine. Is currently participating in another concurrent investigational protocol that is not restricted to data and/or sample collection for patient demographic and/or disease purposes.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>clofarabine Dose Escalation | Drug: clofarabine<br>* Drug given Daily x 14 days and 7 days of rest for 21 day cycle<br>|
| Experimental: Part B<br>Part B is an open-label, replicated cross-over study in which 12 additional patients will be enrolled and treated at the MTD determined in part A to evaluate the effect of food on the PK disposition of oral clofarabine. | Drug: clofarabine<br>* Drug given Daily X 14 days and 7 days of rest for 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated dose levels |  | First Cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile |  | After MTD is established | 
| Food effect on profile |  | After MTD is established | 
| Activity of clofarabine in this dosing regimen |  | Duration of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Clofarabine,, relapsed/refractory MDS,, Myelodysplastic