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

• ClinicalTrials.gov Identifier: NCT01359657
• Recruitment Status: Completed
• First Posted: May 25, 2011
• Last Update Posted: March 16, 2016
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: Anti-CXCR4 (BMS-936564); Biological: Lenalidomide; Biological: Dexamethasone; Biological: Bortezomib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: September 2011
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Determination of maximum tolerated dose [ Time Frame: 42 days in Arm A ]
2. Determination of maximum tolerated dose [ Time Frame: 35 days in Arm B ]

Secondary Outcome Measures :

1. 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 ]
   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
2. 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 ]
3. 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 ]
4. 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 ]
5. 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 ]
6. 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 ]
7. 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 ]
8. 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 ]
9. 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 ]
10. 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 ]
11. 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 ]
12. 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 ]
13. 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 ]
14. 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 ]
15. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Florida

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

United States, Kansas

University Of Kansas Cancer Center And Medical Pavillion

Westwood, Kansas, United States, 66205

United States, Massachusetts

Dana Faber Cancer Institute

Boston, Massachusetts, United States, 02215

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:

BMS clinical trial educational resource 

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01359657
• Other Study ID Numbers: CA212-002
• First Posted: May 25, 2011
• Last Update Posted: March 16, 2016
• Last Verified: July 2015

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; Dexamethasone acetate; Lenalidomide; Bortezomib; BB 1101; Antibodies, Monoclonal; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal