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

NCT01592370 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA209-0392018-001030-17
• Study Type: interventional
• Target: 320
• Locations: 6 countries
• Sites: 43

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.

Conditions

Non-Hodgkin's Lymphoma; Hodgkin Lymphoma; Multiple Myeloma

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort

  approximately up to 4 years

• Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort

  approximately up to 4 years

• Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology

  approximately up to 4 years

• Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver

  approximately up to 4 years

• Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid

  approximately up to 4 years

Secondary Outcomes (19)

• Best Overall 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

• Best Overall Response - Multiple Myeloma Group

  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

• Duration of Response

  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

• Duration of Response - Multiple Myeloma Group

  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

• Progression Free Survival

  From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)

Study Arms (5)

Nivolumab monotherapy (Dose Escalation)

EXPERIMENTAL

Nivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Biological: Nivolumab

Nivolumab + Ipilimumab

EXPERIMENTAL

Nivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Biological: Nivolumab; Biological: Ipilimumab

Nivolumab + Lirilumab

EXPERIMENTAL

Non-randomized Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks Enrollment is closed for this cohort

Biological: Nivolumab; Biological: Lirilumab

Nivo + Dara + Pom + Dexa vs. Nivo + Dara

EXPERIMENTAL

Randomized Nivolumab: Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 \& beyond: 480 mg Day 1 Daratumumab: Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 \& beyond: 16 mg/kg Day 1 Pomalidomide: 4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle Dexamethasone: Weeks without daratumumab dosing: * 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old * 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants \> 75 years old Weeks with daratumumab dosing: * 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old * 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants \> 75 years old Enrollment is closed for this cohort

Biological: Nivolumab; Biological: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone

Daratumumab vs. Nivolumab + Daratumumab

EXPERIMENTAL

Randomized Nivolumab: Cycle 1: 240 mg Day 15 Cycle 2 \& beyond: 480 mg Day 1 Daratumumab: Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 \& beyond: 16 mg/kg Day 1

Biological: Nivolumab; Biological: Daratumumab

Interventions

Nivolumab BIOLOGICAL

Administered by intravenous (IV) infusion

Also known as: BMS-936558, Opdivo

Daratumumab vs. Nivolumab + Daratumumab; Nivo + Dara + Pom + Dexa vs. Nivo + Dara; Nivolumab + Ipilimumab; Nivolumab + Lirilumab; Nivolumab monotherapy (Dose Escalation)

Ipilimumab BIOLOGICAL

Administered by IV infusion

Also known as: Yervoy, BMS-734016, MDX010

Nivolumab + Ipilimumab

Lirilumab BIOLOGICAL

Administered by IV infusion

Also known as: BMS-986015

Nivolumab + Lirilumab

Daratumumab BIOLOGICAL

Administered by IV infusion

Also known as: Darzalex

Daratumumab vs. Nivolumab + Daratumumab; Nivo + Dara + Pom + Dexa vs. Nivo + Dara

Pomalidomide DRUG

Administered PO

Also known as: Pomalyst

Nivo + Dara + Pom + Dexa vs. Nivo + Dara

Dexamethasone DRUG

Administered PO and by IV infusion

Also known as: Intensol

Nivo + Dara + Pom + Dexa vs. Nivo + Dara

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Janssen, LP: collaborator

Study Sites (43)

Local Institution - 0035

Clovis, California, 93611, United States

Location

Division Of Hematology & Oncology Ctr. For Health Sciences

Los Angeles, California, 90095, United States

Location

Local Institution - 0012

Los Angeles, California, 90095, United States

Location

Local Institution - 0017

Aurora, Colorado, 80045, United States

Location

Local Institution - 013

New Haven, Connecticut, 06520, United States

Location

Local Institution - 0023

Orlando, Florida, 32804, United States

Location

Local Institution - 0037

Skokie, Illinois, 60077, United States

Location

Local Institution - 0019

Indianapolis, Indiana, 46202, United States

Location

Local Institution - 0018

Westwood, Kansas, 66205, United States

Location

Local Institution - 0003

Baltimore, Maryland, 21231, United States

Location

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0009

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0015

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0011

Ann Arbor, Michigan, 48109, United States

Location

University Of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0002

Rochester, Minnesota, 55905, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0033

Omaha, Nebraska, 68130, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0014

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0001

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Local Institution - 0028

Columbus, Ohio, 43210, United States

Location

Local Institution - 0006

Portland, Oregon, 97239, United States

Location

OHSU Center for Hematologic Malignancies

Portland, Oregon, 97239, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0007

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Local Institution - 0004

Philadelphia, Pennsylvania, 19111, United States

Location

Huntsman Cancer Institute At The Univ. Of Utah

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 0005

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 0045

Ghent, 9000, Belgium

Location

Local Institution - 0047

Sint-Niklaas, 9100, Belgium

Location

Local Institution

Yvoir, B-5530, Belgium

Location

Local Institution - 0043

Poitiers, Vienne, 86021, France

Location

Local Institution - 0044

Nantes, 44000, France

Location

Local Institution - 0039

Athens, 11528, Greece

Location

Local Institution

Bologna, 40138, Italy

Location

Local Institution

Chorzów, 41-500, Poland

Location

Local Institution - 0040

Poznan, 61-848, Poland

Location

Local Institution - 0049

Warsaw, 02-776, Poland

Location

Local Institution - 0042

Wroclaw, 50-367, Poland

Location

Related Publications (2)

• 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.

  PMID: 27269947 DERIVED

• 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.

  PMID: 25482239 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma

Interventions

Nivolumab; Ipilimumab; lirilumab; daratumumab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2012
• First Posted: May 7, 2012
• Study Start: August 2, 2012
• Primary Completion: September 25, 2020
• Study Completion: July 9, 2024
• Last Updated: October 22, 2025
• Results First Posted: February 17, 2022

Record last verified: 2025-10

Locations

PL (4); BE (3); GR (1); FR (2); US (32); IT (1)