Safety and Pharmacology Study of Sapacitabine to Treat Advanced Leukemias or Myelodysplastic Syndromes

Study Overview
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Brief Summary
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The goal of this safety/pharmacology study is to determine MTD of sapacitabine when administered in patients with advanced leukemias or myelodysplastic syndromes.

Detailed Description
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The goal of this study is to find the highest tolerable dose of sapacitabine that can be given to patients with advanced leukemias or myelodysplastic syndromes.

Official Title
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A Phase I Pharmacologic Study of Oral Sapacitabine in Patients With Advanced Leukemias or Myelodysplastic Syndromes

Conditions
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Leukemias, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: sapacitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with advanced leukemias or myelodysplastic syndromes defined in section 4.1; Eastern Cooperative Oncology Group performance status 0-2; adequate hepatic and renal function; ability to swallow capsules; be at least 2 weeks from prior chemotherapy, radiation therapy, major surgery or other investigational anticancer therapy; and have recovered from prior toxicities. Exclusion Criteria: Patients with known CNS involvement by leukemia; plan to undergo allogeneic bone marrow transplant within 4 weeks; currently on other investigational agents; uncontrolled intercurrent illnesses; pregnant or lactating women; known to be HIV positive

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: Sequential Assignment
Interventional Model Description: The starting dose is (A) 75 mg twice daily x 7 days followed by 14 days of rest or, (B) 375 mg twice daily x 3 consecutive days per week for 2 weeks followed by 7days of rest. Evaluated doses in schedule A: 75mg, 100mg, 125mg, 175mg, 225mg, 275mg, 325mg and 375mg Evaluated doses in schedule B: 375mg, 425mg and 475mg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sapacitabine low dose<br>sapacitabine administered every 12 hours for 7 days followed by 14 days of rest or every 12 hours for 3 consecutive days per week for 2 weeks followed by 7 days of rest in patients with advanced leukemias or myelodysplastic syndromes The starting dose is (A) 75 mg twice daily x 7 days followed by 14 days of rest; Evaluated doses: 75mg, 100mg, 125mg, 175mg, 225mg, 275mg, 325mg and 375mg | Drug: sapacitabine<br> <br> * Other names: CYC682;|
| Experimental: sapacitabine high dose<br>The starting dose is 375 mg twice daily x 3 consecutive days per week for 2 weeks followed by 7days of rest. Evaluated doses: 375mg, 425mg and 475mg | Drug: sapacitabine<br> <br> * Other names: CYC682;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | dose limiting toxicities; during first cycle, each cycle is three weeks | Through study completion, average of 1 year |