Efficacy Study of Oral Sapacitabine to Treat Acute Myeloid Leukemia in Elderly Patients

Study Overview
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Brief Summary
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The objective is to treat elderly AML and MDS patients with sapacitabine.

Detailed Description
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The main objective of this study is to learn which sapacitabine treatment is more likely to keep the cancer in check for at least one year in AML patients who are at least 70 years of age or older and in MDS patients who are at least 60 years of age.

Official Title
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A Randomized Phase 2 Study of Oral Sapacitabine in Elderly Patients With Acute Myeloid Leukemia Previously Untreated or in First Relapse, or Previously Treated Myelodysplastic Syndromes

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Sapacitabine, Arm A
* Drug: Sapacitabine, Arm B
* Drug: Sapacitabine, Arm C
* Drug: Sapacitabine, Arm D
* Drug: sapacitabine, Arm E
* Drug: sapacitabine, Arm F
* Drug: Sapacitabine, Arm G
* Drug: Sapacitabine, Arm H
* Drug: Sapacitabine, Arm I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy or is in first relapse after achieving a complete remission to initial induction, consolidation and/or maintenance therapy or MDS with IPSS scores of intermediate -2 or higher risk risk which has been previously treated with hypomethylating agents Age 70 years or older for AML and 60 years or older for MDS Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate renal function defined as serum creatinine equal to or less than 1.5 x upper limit of normal (ULN) Adequate liver function defined as total bilirubin or direct bilirubin equal to or less than 1.5 x ULN; alanine aminotransferase (ALT or SGPT) equal to or less than 2.5 x ULN (5 x ULN if tumor has affected the liver) Life expectancy reasonably adequate for evaluating the treatment effect Patient must be able to swallow capsules Patients must be at least 2 weeks from prior systemic therapy, radiation therapy, major surgery, or other investigational therapy, and have recovered from clinically significant toxicities of these prior treatments All men and women of reproductive potential must agree to practice effective contraception for 4 weeks prior to study entry, during the entire study period and for one month after the study unless documentation of infertility exists Ability to understand and willingness to sign the informed consent form Exclusion Criteria: AML is of the sub-type of acute promyelocytic leukemia Having received more than one induction systemic therapy for AML or having received a standard dose or high dose ara-C containing regimen for MDS Patients with known central nervous system (CNS) involvement by leukemia Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active cancer(s) other than AML, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients receiving intravenous antibiotics for infections that are under control may be included in this study Known to be HIV-positive

Ages Eligible for Study
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Minimum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A sapacitabine<br>200 mg b.i.d. x 7 days every 3-4 weeks | Drug: Sapacitabine, Arm A<br>* 200 mg b.i.d. x 7 days every 3-4 weeks<br>* Other names: CYC682;|
| Experimental: B sapacitabine<br>300 mg b.i.d. x 7 days every 3 - 4 weeks | Drug: Sapacitabine, Arm B<br>* 300 mg b.i.d. x 7 days every 3 - 4 weeks<br>* Other names: CYC682;|
| Experimental: C sapacitabine<br>400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks | Drug: Sapacitabine, Arm C<br>* 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks<br>* Other names: CYC682;|
| Experimental: D sapacitabine<br>200 mg b.i.d. x 7 consecutive days every 4 weeks | Drug: Sapacitabine, Arm D<br>* 200 mg b.i.d. x 7 consecutive days every 4 weeks<br>* Other names: CYC682;|
| Experimental: E sapacitabine<br>300 mg q.d. x 7 consecutive days every 4 weeks | Drug: sapacitabine, Arm E<br>* 300 mg q.d. x 7 consecutive days every 4 weeks<br>* Other names: CYC682;|
| Experimental: F sapacitabine<br>300 mg b.i.d. x 3 consecutive days per week for 2 weeks every 4 weeks | Drug: sapacitabine, Arm F<br>* 300 mg b.i.d. x 3 consecutive days per week for 2 weeks every 4 weeks<br>* Other names: CYC682;|
| Experimental: G sapacitabine<br>200 mg b.i.d. x 7 consecutive days every 4 weeks | Drug: Sapacitabine, Arm G<br>* 200 mg b.i.d. x 7 consecutive days every 4 weeks<br>* Other names: CYC682;|
| Experimental: H sapacitabine<br>300 mg q.d. x 7 consecutive days every 4 weeks | Drug: Sapacitabine, Arm H<br>* 300 mg q.d. x 7 consecutive days every 4 weeks<br>* Other names: CYC682;|
| Experimental: I sapacitabine<br>100 mg q.d. x 5 consecutive days per week for 2 weeks every 4 weeks | Drug: Sapacitabine, Arm I<br>* 100 mg q.d. x 5 consecutive days per week for 2 weeks every 4 weeks<br>* Other names: CYC682;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Percentage of patients alive for one year measured from the date of randomization | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR and CRi | Complete remission and complete remission without blood count recovery, transfusion requirements, hospitalized days and safety | From date of randomization until study withdrawal or death assessed up to 6 months |