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

Bristol-Myers Squibb (BMS)

Status and phase

Completed

Phase 1

Conditions

Acute Myelogenous Leukemia

Diffuse Large B-Cell Leukemia

Follicular Lymphoma

Chronic Lymphocytic Leukemia

Treatments

Drug: BMS-936564 (Anti-CXCR4)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01120457

CA212-001

Details and patient eligibility

About

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

Enrollment

96 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

96 participants in 4 patient groups

Arm 1: Dose Escalation and Expansion cohort (AML Patients)

Experimental group

Description:

Dose Escalation: BMS-936564 0.3-10 mg/kg solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle) Dose Expansion: BMS-936564 maximum tolerated dose (MTD) based on dose escalation, solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle)

Treatment:

Drug: BMS-936564 (Anti-CXCR4)

Arm 2: Dose Expansion cohort (DLBCL Patient)

Experimental group

Description:

BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)

Treatment:

Drug: BMS-936564 (Anti-CXCR4)

Arm 3: Dose Expansion cohort (CLL Patient)

Experimental group

Description:

BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)