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

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:

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate Bortezomib Lenalidomide

U.S. FDA Resources

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:	December 2013
Estimated Primary Completion Date:	December 2013 (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), 42 days (cycle 1) 28 days subsequent cycles 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, 35 days (cycle 1) 21 days subsequent cycles 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

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), 42 days (cycle 1) 28 days subsequent cycles

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, 35 days (cycle 1) 21 days subsequent cycles

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

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.

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, Massachusetts
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Irene Ghobrial, Site 002 617-582-8313
United States, Missouri
Washington University School Of Medicine	Terminated
St. Louis, Missouri, United States, 63110
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

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

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:	March 28, 2013
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 June 18, 2013