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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01120457
• Other study ID #: CA212-001
• 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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
• Diffuse Large B-Cell Leukemia
• Follicular Lymphoma
• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Follicular

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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