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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01120457
Other study ID # CA212-001
Secondary ID
Status Completed
Phase Phase 1
First received May 7, 2010
Last updated March 5, 2015
Start date August 2010
Est. completion date November 2014

Study information

Verified date January 2015
Source Bristol-Myers Squibb
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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


Recruitment information / eligibility

Status Completed
Enrollment 96
Est. completion date November 2014
Est. primary completion date November 2014
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
BMS-936564 (Anti-CXCR4)


Locations

Country Name City State
United States B. Douglas Smith, M.D. Baltimore Maryland
United States Uab Comprehensive Cancer Center Birmingham Alabama
United States Dana-Farber Cancer Inst Boston Massachusetts
United States Northwestern University Feinberg School Of Medicine Chicago Illinois
United States The University Of Texas Md Anderson Cancer Center Houston Texas
United States Mayo Clinic Jacksonville Florida
United States Uc San Diego Moores Cancer Center La Jolla California
United States Ucla-Division Of Hematology/Oncology Los Angeles California
United States Usc - Norris Comprehensive Cancer Center And Hospital Los Angeles California
United States University Of Washington School Of Medicine Seattle Washington
United States University Of Kansas Cancer Center And Medical Pavillion Westwood Kansas

Sponsors (1)

Lead Sponsor Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety and tolerability as monotherapy Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities Within the first 7 days for AML Yes
Primary Safety and tolerability as monotherapy Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities Within 28 days for the selected B-cell malignancies Yes
Secondary Safety, as measured by vital signs, clinical laboratory tests,ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events ECOG - Eastern Cooperative Oncology Group ECG - Electrocardiograms For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies Yes
Secondary Efficacy- including best overall response (BOR) derived from changes in tumor burden and metabolic response based on FDG-PET (for DLBCL) FDG-PET - fluoro-2-deoxyglucose positron emission tomography DLBCL - Diffuse Large B-Cell Lymphoma For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Immunogenicity measurement for human anti human antibodies (HAHA) -characterizing the immunogenicity of BMS-936564 Subjects will be called as immunogenicity positive/negative to antibodies against BMS-936564 (MDX-1338) using immunogenicity assay, and will be classified as negative, positive baseline, or negative baseline with at least one positive post-treatment. The number and percentage of subjects in each classification will be reported for each dose level. For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Maximum observed serum concentration (Cmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Trough observed serum concentration (Cmin) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Time of maximum observed concentration (Tmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Half life (T-HALF) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Total body clearance(CLT) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Volume of distribution at steady-state (Vss) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Biomarker- characterizing the pharmacodynamic (PD) profiles of BMS-936564 (MDX-1338). The main PD biomarkers are cell trafficking For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
Secondary Exploratory Biomarkers- are detection of apoptosis, cytokine analyses, CXCR4 expression, ZAP-70 and CD38 expression For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies No
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