Clinical trial NCT01592370: An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma
Official title: Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Hodgkin Lymphoma
Multiple Myeloma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Janssen, LP
First posted: 2012-05-07
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the side effects of treatment of the combination of nivolumab and daratumumab in participants with relapsed/refractory multiple myeloma.

Detailed description: NOTE: Currently, this study is only open to nivolumab+daratumumab vs daratumumab monotherapy in multiple myeloma patients.

Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Have received at least 3 prior lines of therapy, including a proteasome inhibitor \[PI\] and an immunomodulatory agent \[IMiD\] OR have disease that is double refractory to a PI and IMiD
* More than 12 weeks post-transplant of your own blood forming stem cells (autologous transplant)
* Have detectable disease measured by a specific protein in your blood and/or urine
* Must consent to bone marrow aspirate or biopsy.

Exclusion Criteria:

* Solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia, or monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome or active plasma cell leukemia
* Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or anti-CD38 antibody, or allogeneic stem cell transplantation
* Seropositive for human immunodeficiency virus (HIV), Hepatitis B surface antigen or Hepatitis C antibody positive (except if HCV-RNA negative), or history of active chronic hepatitis B or C
* History of central nervous system involvement or symptoms suggestive of central nervous system involvement by multiple myeloma

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: Number of Participants That Experienced Drug Related Grade 3-4 AEs
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Number of Participants That Experienced Drug Related Grade 3-4 SAEs
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Number of Participants That Experience Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology
timeFrame: approximately up to 4 years
measure: Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver
timeFrame: approximately up to 4 years
measure: Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid
timeFrame: approximately up to 4 years
Secondary outcomes:
measure: Best Overall Response
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Best Overall Response - Multiple Myeloma Group
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Duration of Response
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to approximately 37 months Nivo Liri: approximately up to 4 years 1 month
measure: Duration of Response - Multiple Myeloma Group
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure: Progression Free Survival
timeFrame: From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
measure: Progression Free Survival Rate
timeFrame: From randomization to the specified timepoints (up to 48 months)
measure: Overall Survival
timeFrame: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to3 years Nivo Liri: approximately up to 4 years 1 month
measure: Number of Participants With PD-L1 Expression
timeFrame: At baseline (prior to start of study treatment)
measure: Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score
timeFrame: From baseline (last measurement before start of study treatment) to last available measurement after start of study treatment (88 weeks for Nivo mono, 93 weeks for nivo+ipi, 25 weeks for nivo+liri)
measure: Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Objective Response Rate in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Duration of Response in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Progression Free Survival in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Cmax in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Tmax in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: Cmin in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: AUC (0-T) in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: AUC (TAU) in the Nivolumab + Daratumumab Cohort
timeFrame: approximately up to 4 years
measure: End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort
timeFrame: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
Other outcomes:
Locations:
city: Clovis
country: United States
facility: Local Institution - 0035
state: California
city: Los Angeles
country: United States
facility: Division Of Hematology & Oncology Ctr. For Health Sciences
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0012
state: California
city: Aurora
country: United States
facility: Local Institution - 0017
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 013
state: Connecticut
city: Orlando
country: United States
facility: Local Institution - 0023
state: Florida
city: Skokie
country: United States
facility: Local Institution - 0037
state: Illinois
city: Indianapolis
country: United States
facility: Local Institution - 0019
state: Indiana
city: Westwood
country: United States
facility: Local Institution - 0018
state: Kansas
city: Baltimore
country: United States
facility: Local Institution - 0003
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0009
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0015
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0011
state: Michigan
city: Ann Arbor
country: United States
facility: University Of Michigan Health System
state: Michigan
city: Rochester
country: United States
facility: Local Institution - 0002
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: Local Institution - 0033
state: Nebraska
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 0014
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0001
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Local Institution - 0028
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0006
state: Oregon
city: Portland
country: United States
facility: OHSU Center for Hematologic Malignancies
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0007
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0004
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute At The Univ. Of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Local Institution - 0005
state: Utah
city: Gent
country: Belgium
facility: Local Institution - 0045
city: Sint-Niklaas
country: Belgium
facility: Local Institution - 0047
city: Yvoir
country: Belgium
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution - 0043
state: Vienne
city: Nantes Cedex 1
country: France
facility: Local Institution - 0044
city: Athens
country: Greece
facility: Local Institution - 0039
city: Bologna
country: Italy
facility: Local Institution
city: Chorzow
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution - 0040
city: Warszawa
country: Poland
facility: Local Institution - 0049
city: Wroclaw
country: Poland
facility: Local Institution - 0042
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, Millenson MM, Cohen AD, Schuster SJ, Lebovic D, Dhodapkar M, Avigan D, Chapuy B, Ligon AH, Freeman GJ, Rodig SJ, Cattry D, Zhu L, Grosso JF, Bradley Garelik MB, Shipp MA, Borrello I, Timmerman J. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016 Aug 10;34(23):2698-704. doi: 10.1200/JCO.2015.65.9789. Epub 2016 Jun 6.
citation: Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22;372(4):311-9. doi: 10.1056/NEJMoa1411087. Epub 2014 Dec 6.