An Exploratory Study to Evaluate the Combination of Elotuzumab and Nivolumab With and Without Pomalidomide in Relapsed Refractory Multiple Myeloma

This research study is studying a combination of targeted therapies as a possible treatment for multiple myeloma (MM).

The drugs involved in this study are:

• Elotuzumab
• Nivolumab
• Pomalidomide
• Dexamethasone

Study Overview

• Status: Withdrawn
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Elotuzumab; Drug: Nivolumab; Drug: Dexamethasone; Drug: Pomalidomide

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the combination works in treating a specific disease. "Investigational" means that the drug combination is being studied.

This study has two parts. Each part tests a different combination of drugs.

• In Part 1 participants will be given elotuzumab and nivolumab.
• In Part 2 participants will be given elotuzumab, nivolumab, pomalidomide, and dexamethasone.

Each of these drugs works in a different way to help the body fight multiple myeloma. The drugs are being tested in different combinations to see if they are more effective when taken together.

Elotuzumab is an antibody, that stimulates the immune system to fight your disease. The FDA (the U.S. Food and Drug Administration) has approved elotuzumab in combination with lenalidomide as a treatment option for this disease.

In this research study, the participant will receive pomalidomide which is an immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight the disease. The FDA has approved pomalidomide as a treatment option for this disease after receiving two other therapies.

Dexamethasone, also FDA approved, is a type of steroid and is usually combined with other chemotherapy for the treatment of blood cancers, such as myeloma and leukemias.

The FDA has not approved nivolumab for this specific disease but it has been approved for other uses, specifically lung cancer. Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer.

In this research study the investigators are looking to see if the combination of elotuzumab, nivolumab, pomalidomide, and dexamethasone is effective in fighting the cancer.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patient ≥ age 18 years
• Patient is able to understand and has given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Patient has been previously diagnosed with MM based on standard International Myeloma Working Group (IMWG) criteria and currently requires treatment.
• Patient must have received at least two previous lines of therapy for multiple myeloma including lenalidomide or thalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib).

• Patient must have demonstrated disease progression on or within 60 days of completion of the last therapy. Patient has measurable disease defined as at least one of the following:

  • Serum M protein ≥ 0.5 g/dL (≥5 g/L)
  • Urine M protein ≥200 mg/24 hours
  • Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Appendix A)
• Negative serum or urine pregnancy test for women of child-bearing potential
• Screening Laboratory parameters:

• Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L). Granulocyte colony-stimulating factor (GCSF) is not permitted during screening to meet eligibility criteria and within 14 days of initiation of therapy

  • Platelet count ≥ 75,000 cells/dL (75 x 109/L) Platelet transfusion is not permitted during screening to meet eligibility criteria and within 14 days of initiation of therapy
  • Hemoglobin ≥ 8.0 g/dl ( red blood cell (RBC) transfusions are permitted during the screening period)
  • Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (Patients with known Gilbert Syndrome are allowed to have total bilirubin < 3.0 mg/dL)
  • Aspartate transaminase (AST, or SGOT) and alanine transaminase (ALT, or SGPT) ≤ 3.0x ULN
  • Estimated creatinine clearance by Cockcroft-Gault formula ≥ 40 mL/min
  • Serum creatinine < 1.5 X ULN. (Appendix C)

Exclusion Criteria:

• Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
• Prior therapy with pomalidomide
• Prior treatment with monoclonal antibodies including elotuzumab
• Prior therapy with anti-programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) agents.
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
• Prior anti-cancer therapy within 14 days.
• Patient has any Grade 3 or > unresolved adverse reaction from previous treatment. Previous allogeneic stem cell transplantation with active graft-versus-host disease (GVHD) or being under immunosuppressive therapy in the last 2 months prior to inclusion in the trial.
• Autologous stem cell transplant if < 12 weeks from enrollment.
• Daily requirement for oral corticosteroids (equivalent to > 10 mg/day prednisone daily) Inhaled or topical corticosteroids are allowed.
• Patient is human immunodeficiency virus (HIV) positive,.
• Patient is Hepatitis B Surface antigen-positive.
• Patient has active hepatitis C infection.
• Patient has an autoimmune disease. (Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger).
• Any clinically significant, uncontrolled medical conditions that, in the treating Investigator's opinion, would impose excessive risk to the patient or may interfere with compliance or interpretation of the study results. Uncontrolled intercurrent illness may include, but is not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations as determined by treating investigator that would limit compliance with study requirements.
• History of erythema multiforme or severe hypersensitivity to prior IMiD's®
• Inability to tolerate thromboprophylaxis
• Known severe intolerance to prior steroid therapy (Grade 3 or above adverse event which was unresponsive to a dose reduction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + Elotuzumab; 22 patients will be entered, If > 4 patients achieve at least a partial response (PR) within 4 cycles an additional 18 patients will be treated.; Nivolumab will be administered intravenously twice per cycle for cycle 1-4; Nivolumab will be administered intravenously once per cycle for cycle 5; Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2; Elotuzumab will be administered intravenously twice per cycle for cycle 3-4; Elotuzumab will be administered intravenously once per cycle for cycle 5	Drug: Elotuzumab; Elotuzumab is an antibody, that stimulates the immune system to fight diseases; Other Names: Empliciti; Drug: Nivolumab; Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer; Other Names: Opdivo
Experimental: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone; Nivolumab will be administered intravenously twice per cycle for cycle 1-4; Nivolumab will be administered intravenously once per cycle for cycle 5; Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2; Elotuzumab will be administered intravenously twice per cycle for cycle 3-4; Elotuzumab will be administered intravenously once per cycle for cycle 5; Pomalidomide will be administered for 21 days per cycle; Dexamethasone will be administered weekly	Drug: Elotuzumab; Elotuzumab is an antibody, that stimulates the immune system to fight diseases; Other Names: Empliciti; Drug: Nivolumab; Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer; Other Names: Opdivo; Drug: Dexamethasone; Dexamethasone, a corticosteroid, is similar to a natural hormone produced by adrenal glands. It relieves inflammation.; Other Names: Maxidex; Drug: Pomalidomide; Pomalidomide which is an immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight diseases.; Other Names: Pomalyst

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response Rate	2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	2 years
Overall Survival	2 years
Duration of Response	2 years
Time to Response	2 years
The Rate of Clinical Benefit Response (CBR)	2 years
Time to Treatment Failure	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Jacob Laubach, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Dexamethasone; Pomalidomide; Nivolumab; Elotuzumab
• Other Study ID Numbers: 16-645

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No