Anti-CXCR4 (BMS-936564) Alone and in Combination With Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma

This study is currently recruiting participants.
Verified January 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01359657
First received: May 11, 2011
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine 1) the safety and tolerability of multiple intravenous doses of anti-CXCR4 (BMS-936564) as monotherapy and as combination, and 2) the maximum tolerated dose (MTD) of BMS-936564 in combination with Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in subjects with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Biological: Anti-CXCR4 (BMS-936564)
Biological: Lenalidomide
Biological: Dexamethasone
Biological: Bortezomib
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 1b, Open-label, Multicenter Study of (BMS-936564) in Combination With Lenalidomide (Revlimid) Plus Low-dose Dexamethasone, or With Bortezomib (Velcade) Plus Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Determination of maximum tolerated dose [ Time Frame: 42 days in Arm A ] [ Designated as safety issue: Yes ]
  • Determination of maximum tolerated dose [ Time Frame: 35 days in Arm B ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety and tolerability will be analyzed for all patients. Safety endpoints will be based on adverse event reports, and include frequent adverse event (AE)s, serious adverse event (SAE)s and lab abnormalities [ Time Frame: Safety will be evaluated up to 2 years ] [ Designated as safety issue: Yes ]
    Additionally safety will be measures using vital signs, electrocardiogram (ECG)s, Multiple gated acquisition scan (MUGA) or echocardiograms (ECHO), physical examination, radiology exams, skeletal survey and clinical laboratory tests

  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be maximum observed concentration (Cmax) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be trough observed concentration (Cmin) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be time of maximum observed concentration (Tmax) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be area under the concentration-time curve in one dosing interval (AUC (TAU)) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be half-life (T-Half) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be total body clearance (CLT) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be volume of distribution at steady-state (Vss) [ Time Frame: PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B ] [ Designated as safety issue: No ]
  • Individual tumor responses as defined by the International Myeloma Working Group Uniform Response Criteria (IMWG) for Multiple Myeloma (MM) will be used to monitor efficacy. For this assessment blood urine, and/or bone marrow assessment will be used [ Time Frame: within 28 days prior to first dose ] [ Designated as safety issue: Yes ]
  • Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow will not be collected unless to confirm complete response (CR)) [ Time Frame: On Cycle 1 day 14 ] [ Designated as safety issue: Yes ]
  • Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow assessment will be collected during screening period, at end of cycle 1, end of cycle 4 and to confirm CR ) [ Time Frame: At end of each Cycle ] [ Designated as safety issue: Yes ]
  • Samples will be collected to characterize immunogenicity [ Time Frame: For Arm A, blood samples will be collected prior to dosing administration on Cycle 1 (predose & Days 1, 15, & 29), Cycle 2 Day 1, Cycle 3 Day 1; & Day 1 of Cycle 6 & every 6 cycles, end of treatment, & at 3 & 6 month follow-up visits, if available ] [ Designated as safety issue: No ]
  • Samples will be collected to characterize immunogenicity [ Time Frame: For Arm B, blood samples will be collected at Cycle 1 (predose & Days 1, 15, & 29), Cycle 2 Day 1, Cycle 3 Day 1; Cycle 4 Day 1; & Day 1 on Cycle 8 & every 8 cycles, if available, end of treatment, & at 3 & 6 month follow-up visits, if available ] [ Designated as safety issue: No ]
  • Baseline level of cytokines/chemokines/growth factors will be determined, but not limited to SDF1 in peripheral blood and bone marrow [ Time Frame: Sample will be collected within 28 days prior to first dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: September 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Anti-CXCR4 (BMS-936564)+Lenalidomide+Dexamethasone Biological: Anti-CXCR4 (BMS-936564)
Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 42 days (cycle 1) 28 days subsequent cycles
Other Name: Anti-CXCR4
Biological: Lenalidomide
Tablets, per os (by mouth route of administration) (P.O), 25 mg, daily for 21 days (Day 15-35 in cycle 1; Day 1-21 in subsequent cycles), no dosing in Cycle 1, Cycle 2 +:daily dosing from Day 1-21
Other Name: Revlimid®
Biological: Dexamethasone
Tablets, per os (by mouth route of administration) (P.O), 40 mg, administered with Lenalidomide once every 7 days, 42 days (cycle 1) 28 days subsequent cycles
Experimental: Arm B: Anti-CXCR4 (BMS-936564)+Bortezomib+Dexamethasone Biological: Anti-CXCR4 (BMS-936564)
Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 35 days (cycle 1) 21 days subsequent cycles
Other Name: Anti-CXCR4
Biological: Bortezomib
Intravenous (IV), 1.3 mg/m2, administered on day 15, 18, 22, 25 in cycle 1, then on Day 1, 4, 8, 11 in subsequent cycles, no dosing in Cycle 1, Cycle 2 +:dosing on Day 1, 4, 8, 11
Other Name: Velcade®
Biological: Dexamethasone
Tablets, per os (by mouth route of administration) (P.O), 40 mg, administered on the day of (and the day after) Bortezomib infusion, 35 days (cycle 1) 21 days subsequent cycles

  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:

  • Subjects must have confirmed diagnosis of multiple myeloma with measurable disease Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma.
  • Disease must be assessed within 28 days prior to treatment initiation.
  • Subjects must have evidence of relapsed or relapsed/refractory disease.
  • Subjects must have received at least 2 prior regimens for multiple myeloma.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2.
  • Subjects must have received last treatment (ie, chemotherapy, radiotherapy, biological, immunotherapy or investigational agent [therapeutic or diagnostic]) at least 14 days prior to treatment initiation. The last treatment of systemically absorbed steroids must be at least 2 weeks or 5 half lives (whichever is shorter) before the first dose of BMS-936564.

Exclusion Criteria:

  • A serious uncontrolled medical disorder or active infection.
  • Current or recent (within 3 months) gastrointestinal disease or condition that could impact the absorption of orally-administered drug.
  • Inability to swallow oral medication.
  • Uncontrolled or significant heart disease.
  • Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01359657

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Rachid Baz, Site 001    813-745-1676      
United States, Kansas
University Of Kansas Cancer Center And Medical Pavillion Recruiting
Westwood, Kansas, United States, 66205
Contact: Brea Lipe, Site 007    913-588-2314      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Irene Ghobrial, Site 002    617-582-8313      
United States, Washington
University Of Washington School Of Medicine Recruiting
Seattle, Washington, United States, 98195
Contact: Pamela S Becker, Site 003    206-543-3207      
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: NCT01359657     History of Changes
Other Study ID Numbers: CA212-002
Study First Received: May 11, 2011
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
Relapsed
Refractory

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on April 22, 2014