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
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 |
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
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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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 |
Lead Sponsor | Collaborator |
---|---|
Bristol-Myers Squibb |
United States,
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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