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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Anti-CXCR4 (BMS-936564)

Lenalidomide

Dexamethasone

Anti-CXCR4 (BMS-936564)

Bortezomib

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Relapsed, Refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

H. Lee Moffitt Cancer Center & Research Institute
University Of Kansas Cancer Center And Medical Pavillion
Dana Faber Cancer Institute
University Of Washington School Of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A: Anti-CXCR4 (BMS-936564)+Lenalidomide+Dexamethasone

Arm B: Anti-CXCR4 (BMS-936564)+Bortezomib+Dexamethasone

Arm Description

Outcomes

Primary Outcome Measures

Determination of maximum tolerated dose

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

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)

Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be trough observed concentration (Cmin)

Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be time of maximum observed concentration (Tmax)

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))

Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be half-life (T-Half)

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))

Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be total body clearance (CLT)

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)

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

Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow will not be collected unless to confirm complete response (CR))

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 )

Samples will be collected to characterize immunogenicity

Baseline level of cytokines/chemokines/growth factors will be determined, but not limited to SDF1 in peripheral blood and bone marrow

Full Information

NCT ID

NCT01359657

First Posted

May 11, 2011

Last Updated

March 15, 2016

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01359657

Brief Title

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

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

September 2011 (undefined)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

Relapsed, Refractory

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

46 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Anti-CXCR4 (BMS-936564)+Lenalidomide+Dexamethasone

Arm Type

Experimental

Arm Title

Arm B: Anti-CXCR4 (BMS-936564)+Bortezomib+Dexamethasone

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Anti-CXCR4 (BMS-936564)

Other Intervention Name(s)

Anti-CXCR4

Intervention Description

Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 42 days (cycle 1) 28 days subsequent cycles

Intervention Type

Biological

Intervention Name(s)

Lenalidomide

Other Intervention Name(s)

Revlimid®

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Dexamethasone

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Anti-CXCR4 (BMS-936564)

Other Intervention Name(s)

Anti-CXCR4

Intervention Description

Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 35 days (cycle 1) 21 days subsequent cycles

Intervention Type

Biological

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade®

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Dexamethasone

Intervention Description

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

Primary Outcome Measure Information:

Title

Determination of maximum tolerated dose

Time Frame

42 days in Arm A

Title

Determination of maximum tolerated dose

Time Frame

35 days in Arm B

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

Safety will be evaluated up to 2 years

Title

Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be maximum observed concentration (Cmax)

Time Frame