A Study of BMS-863233 in Patients With Hematologic Cancer

Study Overview
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Brief Summary
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To determine safety, tolerability and maximum tolerated dose of BMS-63233/XL413 in subjects with Refractory Hematologic Cancer

Official Title
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A Phase 1/2, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-863233 in Subjects With Refractory Hematologic Malignancies

Conditions
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Refractory Hematologic Cancer

Intervention / Treatment
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* Drug: Cdc7-inhibitor (BMS-863233)
* Drug: Cdc7-inhibitor (BMS-863233)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AML by current WHO diagnostic criteria, any FAB type (except APML), Refractory ALL, Accelerated/blast phase CML and Refractory MDS with total IPSS score of 2 or higher ECOG performance status <= 2 Accessible for treatment, PK sample collection and required study follow-up Total Bilirubin ≤ 1.5 x ULN and ALT, AST ≤ 3 x ULN Exclusion Criteria: Women who are pregnant or breastfeeding Subjects with Acute Promyelocytic leukemia disease or CNS leukemia disease) Hyperleukocytosis (defined as peripheral WBC >50,000/uL) Treatment with any other investigational agent for any indication within 30 days of protocol enrollment Subjects a history of gastrointestinal disease Subjects less than four weeks from allogenic or autologous stem cell transplant infusion

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 |
| --- | --- |
| Active Comparator: Cdc7-inhibitor (A)<br> | Drug: Cdc7-inhibitor (BMS-863233)<br>* Tablets, Oral, QD x 14 days until MTD is achieved, 14 days per 28 day cycle/QD, 12 months<br>* Other names: BMS-863233;|
| Active Comparator: Cdc7-inhibitor (B)<br> | Drug: Cdc7-inhibitor (BMS-863233)<br>* Tablets, Oral, MTD of Cdc7-inhibitor (A) Arm, QD x 7 days until MTD achieved, 7 days per 21 day cycle/QD, 12 months<br>* Other names: BMS-863233;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine maximum tolerated dose and anti-tumor activity of BMS-863233/XL413 when administered to subjects with refractory Hematologic Cancer |  | Every 21 or 28 days until maximum tolerated dose is reached | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety of BMS-863233/XL413 when administered to subjects with refractory Hematologic Cancer |  | Every 21 or 28 days until the MTD is reached | 
| To determine the pharmacokinetics of BMS-863233/XL413 when administered to subjects with refractory Hematologic Cancer |  | Every 21 or 28 days until the MTD is reached | 
| To determine the anti-tumor activity of BMS-863233/XL413 when administered to subjects with refractory Hematologic Cancer |  | Every 21 or 28 days until the MTD is reached |