An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01592370
• Other study ID #: CA209-039
• Secondary ID: 2018-001030-17
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 2, 2012
• Est. completion date: December 22, 2023

Study information

• Verified date: September 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 316
• Est. completion date: December 22, 2023
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Lymphoma
• Lymphoma
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Non-Hodgkin's Lymphoma

Intervention

Biological:
• Nivolumab
Administered by intravenous (IV) infusion
• Ipilimumab
Administered by IV infusion
• Lirilumab
Administered by IV infusion
• Daratumumab
Administered by IV infusion

Drug:
• Pomalidomide
Administered PO
• Dexamethasone
Administered PO and by IV infusion

Locations

Country	Name	City	State
Belgium	Local Institution - 0045	Gent
Belgium	Local Institution - 0047	Sint-Niklaas
Belgium	Local Institution	Yvoir
France	Local Institution - 0044	Nantes Cedex 1
France	Local Institution - 0043	Poitiers	Vienne
Greece	Local Institution - 0039	Athens
Italy	Local Institution	Bologna
Poland	Local Institution	Chorzow
Poland	Local Institution - 0040	Poznan
Poland	Local Institution - 0049	Warszawa
Poland	Local Institution - 0042	Wroclaw
United States	Local Institution - 0011	Ann Arbor	Michigan
United States	University Of Michigan Health System	Ann Arbor	Michigan
United States	Local Institution - 0017	Aurora	Colorado
United States	Local Institution - 0003	Baltimore	Maryland
United States	The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Local Institution - 0009	Boston	Massachusetts
United States	Local Institution - 0015	Boston	Massachusetts
United States	Local Institution - 0035	Clovis	California
United States	Local Institution - 0028	Columbus	Ohio
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Local Institution - 0014	Hackensack	New Jersey
United States	Local Institution - 0019	Indianapolis	Indiana
United States	Division Of Hematology & Oncology Ctr. For Health Sciences	Los Angeles	California
United States	Local Institution - 0012	Los Angeles	California
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Local Institution - 0001	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Local Institution - 0033	Omaha	Nebraska
United States	Local Institution - 0023	Orlando	Florida
United States	Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Local Institution - 0004	Philadelphia	Pennsylvania
United States	Local Institution - 0007	Philadelphia	Pennsylvania
United States	Local Institution - 0006	Portland	Oregon
United States	OHSU Center for Hematologic Malignancies	Portland	Oregon
United States	Local Institution - 0002	Rochester	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Huntsman Cancer Institute At The Univ. Of Utah	Salt Lake City	Utah
United States	Local Institution - 0005	Salt Lake City	Utah
United States	Local Institution - 0037	Skokie	Illinois
United States	Local Institution - 0018	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Janssen, LP

Countries where clinical trial is conducted

United States,  Belgium,  France,  Greece,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants That Experienced Drug Related Grade 3-4 AEs	Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.	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
Primary	Number of Participants That Experienced Drug Related Grade 3-4 SAEs	Number and percent of participants that experienced drug related Grade 3-4 SAEs occurring up to 100 days after the last dose of study drug.	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
Primary	Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver	Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.	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
Primary	Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid		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
Primary	Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Primary	Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Primary	Number of Participants That Experience Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Primary	Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology		approximately up to 4 years
Primary	Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver		approximately up to 4 years
Primary	Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid		approximately up to 4 years
Secondary	Best Overall Response	the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.; Measured in Complete Response and Partial Response	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
Secondary	Best Overall Response - Multiple Myeloma Group	the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.	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
Secondary	Duration of Response	the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.; Measured in Complete Remission and Partial Remission	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
Secondary	Duration of Response - Multiple Myeloma Group	the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.; Measured in Complete Response and Partial Response	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
Secondary	Progression Free Survival	Progression free survival (PFS) is defined as the time between date of randomization and date of progression or death, whichever occurs first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Subjects who did not progress or die were censored on the date of their last efficacy assessment.	From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
Secondary	Progression Free Survival Rate	The percentage of participants remaining progression free at the specified timepoints (up to 48 Months)	From randomization to the specified timepoints (up to 48 months)
Secondary	Overall Survival	The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method	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
Secondary	Number of Participants With PD-L1 Expression	Number of Participants with PD-L1 expression in the following categories; baseline PD-L1 expression = 1%; baseline PD-L1 expression < 1%; without PD-L1 quantifiable at baseline	At baseline (prior to start of study treatment)
Secondary	Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score	mSWAT is a scoring technique involving the direct assessment of the percentage of body-surface-area (BSA) affected by skin lesions.; There are 12 body regions (each one assigned a different percentage of BSA). For each body region, the assigned BSA percentage is multiplied by a factor weighing the type and severity of lesion observed (patch= x1, plaque = x2, tumor= x4).; The sum of the individual body region sub-scores is then summed to generate the final mSWAT score, which ranges from 0 (best outcome) to 400 (worst outcome).	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)
Secondary	Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort	Time to MRD Negativity status in specific NGS and NGF sensitivity levels	approximately up to 4 years
Secondary	Objective Response Rate in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Secondary	Duration of Response in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Secondary	Progression Free Survival in the Nivolumab + Daratumumab Cohort		approximately up to 4 years
Secondary	Cmax in the Nivolumab + Daratumumab Cohort	Maximum observed serum concentration	approximately up to 4 years
Secondary	Tmax in the Nivolumab + Daratumumab Cohort	Time of maximum observed serum concentration	approximately up to 4 years
Secondary	Cmin in the Nivolumab + Daratumumab Cohort	Serum concentration achieved at the end of dosing interval (trough concentration)	approximately up to 4 years
Secondary	AUC (0-T) in the Nivolumab + Daratumumab Cohort	Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration	approximately up to 4 years
Secondary	AUC (TAU) in the Nivolumab + Daratumumab Cohort	Area under the concentration-time curve in one dosing interval	approximately up to 4 years
Secondary	End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort	Serum concentration achieved at the end of study drug infusion	Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form