Clinical trial NCT01120457: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Diffuse Large B-Cell Leukemia
Chronic Lymphocytic Leukemia
Follicular Lymphoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-05-11
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility 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

Primary outcomes:
measure: Safety and tolerability as monotherapy
timeFrame: Within the first 7 days for AML
measure: Safety and tolerability as monotherapy
timeFrame: Within 28 days for the selected B-cell malignancies
Secondary outcomes:
measure: Safety, as measured by vital signs, clinical laboratory tests,ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events
timeFrame: 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
measure: Efficacy- including best overall response (BOR) derived from changes in tumor burden and metabolic response based on FDG-PET (for DLBCL)
timeFrame: 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
measure: Immunogenicity measurement for human anti human antibodies (HAHA) -characterizing the immunogenicity of BMS-936564
timeFrame: 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
measure: Maximum observed serum concentration (Cmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: Trough observed serum concentration (Cmin) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: Time of maximum observed concentration (Tmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Half life (T-HALF) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: Total body clearance(CLT) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: Volume of distribution at steady-state (Vss) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time
timeFrame: 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
measure: Biomarker- characterizing the pharmacodynamic (PD) profiles of BMS-936564 (MDX-1338). The main PD biomarkers are cell trafficking
timeFrame: 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
measure: Exploratory Biomarkers- are detection of apoptosis, cytokine analyses, CXCR4 expression, ZAP-70 and CD38 expression
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uab Comprehensive Cancer Center
state: Alabama
city: La Jolla
country: United States
facility: Uc San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Usc - Norris Comprehensive Cancer Center And Hospital
state: California
city: Los Angeles
country: United States
facility: Ucla-Division Of Hematology/Oncology
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School Of Medicine
state: Illinois
city: Westwood
country: United States
facility: University Of Kansas Cancer Center And Medical Pavillion
state: Kansas
city: Baltimore
country: United States
facility: B. Douglas Smith, M.D.
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Inst
state: Massachusetts
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University Of Washington School Of Medicine
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: