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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01120457
First received: May 7, 2010
Last updated: November 13, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Acute Myelogenous Leukemia
Diffuse Large B-Cell Leukemia
Chronic Lymphocytic Leukemia
Follicular Lymphoma
Drug: BMS-936564 (Anti-CXCR4)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety and tolerability as monotherapy [ Time Frame: Within the first 7 days for AML ] [ Designated as safety issue: Yes ]
    Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities

  • Safety and tolerability as monotherapy [ Time Frame: Within 28 days for the selected B-cell malignancies ] [ Designated as safety issue: Yes ]
    Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities


Secondary Outcome Measures:
  • Safety, as measured by vital signs, clinical laboratory tests,ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    ECOG - Eastern Cooperative Oncology Group ECG - Electrocardiograms

  • Efficacy- including best overall response (BOR) derived from changes in tumor burden and metabolic response based on FDG-PET (for DLBCL) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    FDG-PET - fluoro-2-deoxyglucose positron emission tomography DLBCL - Diffuse Large B-Cell Lymphoma

  • Immunogenicity measurement for human anti human antibodies (HAHA) -characterizing the immunogenicity of BMS-936564 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Maximum observed serum concentration (Cmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Trough observed serum concentration (Cmin) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Time of maximum observed concentration (Tmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Half life (T-HALF) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Total body clearance(CLT) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady-state (Vss) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Biomarker- characterizing the pharmacodynamic (PD) profiles of BMS-936564 (MDX-1338). The main PD biomarkers are cell trafficking [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Exploratory Biomarkers- are detection of apoptosis, cytokine analyses, CXCR4 expression, ZAP-70 and CD38 expression [ Time Frame: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 82
Study Start Date: June 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Dose Escalation and Expansion cohort (AML Patients)

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)

Drug: BMS-936564 (Anti-CXCR4)
Other Name: MDX-1338
Experimental: Arm 2: Dose Expansion cohort (DLBCL Patient)
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)
Drug: BMS-936564 (Anti-CXCR4)
Other Name: MDX-1338
Experimental: Arm 3: Dose Expansion cohort (CLL Patient)
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)
Drug: BMS-936564 (Anti-CXCR4)
Other Name: MDX-1338
Experimental: Arm 4: Dose Expansion cohort (FL Patient)
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)
Drug: BMS-936564 (Anti-CXCR4)
Other Name: MDX-1338

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120457

Locations
United States, Alabama
Uab Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, California
Moores Ucsd Cancer Center
La Jolla, California, United States, 92093
Ucla-Division Of Hematology/Oncology
Los Angeles, California, United States, 90095
Usc - Norris Comprehensive Cancer Center And Hospital
Los Angeles, California, United States, 90033
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, United States, 60611
United States, Kansas
University Of Kansas Cancer Center And Medical Pavillion
Westwood, Kansas, United States, 66205
United States, Maryland
B. Douglas Smith, M.D.
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana-Farber Cancer Inst
Boston, Massachusetts, United States, 02215
United States, Texas
The University Of Texas Md Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
University Of Washington School Of Medicine
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01120457     History of Changes
Other Study ID Numbers: CA212-001
Study First Received: May 7, 2010
Last Updated: November 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 23, 2014