First in Human Study to Determine the Safety, Tolerability and Preliminary Efficacy of an Anti-CXCR4 Antibody in Subjects With Acute Myelogenous Leukemia and Selected B-cell Cancers

A Phase 1, Open-label, Multicenter Study of BMS-936564 (MDX-1338) in Subjects With Relapsed Acute Myelogenous Leukemia and Selected B-cell Malignancies

The purpose of this study is to assess the safety and tolerability of BMS-936564 (MDX-1338) in relapsed Acute myelogenous leukemia (AML) and other selected B-cell cancers and to determine the maximum tolerated dose (MTD) of the drug alone in relapsed/refractory AML

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

A. Common to All Indications:

• Life expectancy at least 12 weeks
• ECOG Performance Status of 0-2

B. For Acute myelogenous leukemia (AML) Subjects:

• First Relapse and primary induction failure in AML (M3 excluded)
• Secondary AML subjects from myelodysplastic syndrome (MDS) or prior chemotherapy are eligible. MDS-only subjects are not eligible

C. For Follicular Lymphoma (FL), Diffuse Large B-Cell Lymphoma (DLBCL) Subjects:

• Must be at least 4 weeks (for FL) or 2 weeks (for DLBCL) since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy
• Ability to undergo tumor biopsy pre-treatment and at end of monotherapy period (though not mandatory for all subjects)
• Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease

D. For Chronic lymphocytic leukemia (CLL) Subjects:

• Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease
• Must be at least 4 weeks since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy, including corticosteroids

Exclusion Criteria:

A. Common to All indications:

• Prior anti-CXCR4 therapy including BMS-936564 (MDX-1338)
• Less than 3 months from prior hematopoietic stem cell transplant
• Presence of active graft versus host disease

B. For AML Subjects:

• Acute promyelocytic leukemia (M3)
• Left ventricular ejection fraction < institutional limits of normal

C. For FL, DLBCL Subjects:

• (For DLBCL): Inadequate renal function defined as creatinine clearance (by Cockcroft-Gault formula) < 60 mL/min
• Major surgery, not related to debulking procedures, within 21 days of first dose
• Myocardial infarction within 6 months prior to screening or Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
• Myelodysplastic syndrome (MDS)

D. For CLL Subjects:

• No progression to more aggressive B-cell cancers, such as Richter's syndrome
• Major surgery within 21 days of Cycle 1, Day 1. Patients undergoing debulking procedures and minor surgery are allowed after a recovery period, in the judgment of the Investigator
• Myocardial infarction within 6 months prior to screening Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia