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: September 22, 2014
Last verified: May 2014

May 7, 2010
September 22, 2014
June 2010
October 2014   (final data collection date for primary outcome measure)
  • 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
Determination of Maximum Tolerated Dose (MTD). The MTD is defined as no more than 1 out of 6 subjects experience a Dose Limiting Toxicity (DLT) [ Time Frame: 21-28 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01120457 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety, as measured by vital signs, clinical laboratory tests, bone marrow tests, immunogenicity, ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events, and concomitant medications [ Time Frame: Up to 28 days from each treatment cycle ] [ Designated as safety issue: Yes ]
  • Evaluate preliminary efficacy by Objective Response in subjects treated with MDX1338/BMS-936564 as monotherapy & in combination of chemotherapy. Leukemia response evaluated at the end of each cycle using AML International Working Group (IWG) 2003 [ Time Frame: Up to 28 days from each treatment cycle ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
A Phase 1, Open-label, Multicenter Study of BMS-936564 (MDX-1338) in Subjects With Relapsed Acute Myelogenous Leukemia and Selected B-cell Malignancies

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

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myelogenous Leukemia
  • Diffuse Large B-Cell Leukemia
  • Chronic Lymphocytic Leukemia
  • Follicular Lymphoma
Drug: BMS-936564 (Anti-CXCR4)
Other Name: MDX-1338
  • 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)

    Intervention: Drug: BMS-936564 (Anti-CXCR4)
  • 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)
    Intervention: Drug: BMS-936564 (Anti-CXCR4)
  • 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)
    Intervention: Drug: BMS-936564 (Anti-CXCR4)
  • 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)
    Intervention: Drug: BMS-936564 (Anti-CXCR4)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
82
October 2014
October 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01120457
CA212-001
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP