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

NCT03227432 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 16-645
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Response Rate

  2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  6 months

Secondary Outcomes (6)

• The Rate of Clinical Benefit Response (CBR)

  2 years

• Time to Response

  2 years

• Duration of Response

  2 years

• Progression Free Survival

  2 years

• Overall Survival

  2 years

Study Arms (2)

Nivolumab + Elotuzumab

EXPERIMENTAL

* 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; Drug: Nivolumab

Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone

EXPERIMENTAL

* 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: Dexamethasone; Drug: Pomalidomide; Drug: Elotuzumab; Drug: Nivolumab

Interventions

Dexamethasone DRUG

Dexamethasone, a corticosteroid, is similar to a natural hormone produced by adrenal glands. It relieves inflammation.

Also known as: Maxidex

Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone

Pomalidomide DRUG

Pomalidomide which is an immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight diseases.

Also known as: Pomalyst

Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone

Elotuzumab DRUG

Elotuzumab is an antibody, that stimulates the immune system to fight diseases

Also known as: Empliciti

Nivolumab + Elotuzumab; Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone

Nivolumab DRUG

Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer

Also known as: Opdivo

Nivolumab + Elotuzumab; Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; pomalidomide; elotuzumab; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jacob Laubach, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 24, 2017
• Study Start: December 1, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2024
• Last Updated: August 14, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)