Clinical trial NCT01359657: Anti-CXCR4 (BMS-936564) Alone and in Combination With Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Relapsed
Refractory
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-05-25
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Determination of maximum tolerated dose
timeFrame: 42 days in Arm A
measure: Determination of maximum tolerated dose
timeFrame: 35 days in Arm B
Secondary outcomes:
measure: 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
timeFrame: Safety will be evaluated up to 2 years
measure: Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be maximum observed concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be trough observed concentration (Cmin)
timeFrame: 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
measure: Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be time of maximum observed concentration (Tmax)
timeFrame: 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
measure: 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))
timeFrame: 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
measure: Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be half-life (T-Half)
timeFrame: 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
measure: 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))
timeFrame: 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
measure: Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be total body clearance (CLT)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: 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
timeFrame: within 28 days prior to first dose
measure: Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow will not be collected unless to confirm complete response (CR))
timeFrame: On Cycle 1 day 14
measure: 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 )
timeFrame: At end of each Cycle
measure: Samples will be collected to characterize immunogenicity
timeFrame: 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
measure: Samples will be collected to characterize immunogenicity
timeFrame: 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
measure: Baseline level of cytokines/chemokines/growth factors will be determined, but not limited to SDF1 in peripheral blood and bone marrow
timeFrame: Sample will be collected within 28 days prior to first dose
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Westwood
country: United States
facility: University Of Kansas Cancer Center And Medical Pavillion
state: Kansas
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Seattle
country: United States
facility: University Of Washington School Of Medicine
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: