A Phase II Trial If Nivolumab, Lenalidomide and Dexamethasone in High Risk Smoldering Myeloma

NCT02903381 | Completed Phase 2 Results DMC

• 2 other identifiers: 16-242CA209-607
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating a new drug called "nivolumab" as a possible treatment for smoldering multiple myeloma in order to prevent or postpone development of active multiple myeloma. \- Patients with smoldering multiple myeloma do not have symptoms but are at risk for progressing to active multiple myeloma. Multiple myeloma is a cancer of the plasma cell, which is an important part of the immune system. Patients with active multiple myeloma generally require treatment.

Conditions

Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 2 Year Progression Free Percent

  The primary endpoint will be the 2-year progression-free percent and will be reported with corresponding 90% confidence interval. All patients who have received one dose of study treatment will be included for the analysis, including those who die or are lost to follow-up before 2 years. Progression is defined as ≥ 25% increase and an absolute increase of ≥ 0.5g/dL from their nadir in their serum or urine m-spike or FLC with no CRAB features attributable to MM progression.

  2 Year

Secondary Outcomes (7)

• Objective Response Percent

  2 Years

• Time to Progression Probability at 2-years

  Baseline to documented progression, up to 24 months post initiation of therapy.

• Duration of Response Probability at 2-years

  time from objective response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died, up to 24 months post initiation of therapy.

• Progression Free Survival (PFS) Probability at 2-years

  Baseline to disease progression or death from any cause, censored at date last known progression free for those who have not progressed or died, up to 24 months post initiation of therapy.

• Overall Survival Probability at 2-years

  Baseline to death or date last known alive, up to 24 months post initiation of therapy.

Study Arms (1)

Nivolumab, Lenalidomide, Dexamethasone

EXPERIMENTAL

* A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months.

Drug: Nivolumab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Nivolumab DRUG

Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and

Also known as: Opdivo®

Nivolumab, Lenalidomide, Dexamethasone

Lenalidomide DRUG

Oral, predetermined dosage, Days 1-21 of cycle 1-12

Also known as: Revlimid

Nivolumab, Lenalidomide, Dexamethasone

Dexamethasone DRUG

Oral, Days 1, 8, 15 of cycle 1-6

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex

Nivolumab, Lenalidomide, Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Age 18 years.
• Must meet criteria of high risk smoldering MM based on the criteria described below:
• \-- Definition of high-risk SMM:
• \--- Bone marrow clonal plasma cells ≥10% and ≤60% and any one or more of the following:
• Serum M protein ≥3.0g/dL (IgA, IgG, IgM, or IgD)
• IgA SMM
• Immunoparesis with reduction of two uninvolved immunoglobulin isotypes
• Serum involved/uninvolved free light chain ratio ≥8 (but less than 100)
• \----- Free Light Chain Smoldering Myeloma patients as defined in section 2.4 are not excluded
• Progressive increase in M protein level (Evolving type of SMM)
• \----- Increase in serum monoclonal protein by ≥10% on two successive evaluations within a 6 month period
• Bone marrow clonal plasma cells 50-60%
• Abnormal plasma cell immunophenotype (≥95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes
• t (4;14) or del 17p or 1q gain
• Increased circulating plasma cells

You may not qualify if:

• No evidence of CRAB criteria\* or new criteria of active MM which including the following:
• Increased calcium levels (corrected serum calcium \>0.25 mmol/dL above the upper limit of normal or \>.275 mmol/dL) related to MM
• Renal insufficiency (attributable to MM)
• Anemia (Hb 2g/dL below the lower limit of normal or \<10g/dL) related to MM
• Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)
• Bone marrow plasma cells ≥60%
• MRI with two or more focal lesions that are at least 5 mm or greater in size --- \*Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 2 years of 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.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune pneumonitis, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia, Gravis). Patients with Hashimoto's thyroiditis are eligible to go on study.
• Pregnant or nursing women will be excluded from the study because lenalidomide is an agent with the potential for teratogenic or abortifacient effects.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab or lenalidomide.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Major surgery within 4 weeks before enrollment.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator
• Multiple Myeloma Research Consortium: collaborator
• Blood Cancer Research Partnership: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

Nivolumab; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Irene Ghobrial
• Organization: Dana-Farber Cancer Institute

irene_ghobrial@dfci.harvard.edu

617-632-4198

Study Officials

• Irene M. Ghobrial, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 16, 2016
• Study Start: October 20, 2016
• Primary Completion: June 28, 2018
• Study Completion: September 16, 2021
• Last Updated: June 13, 2023
• Results First Posted: June 13, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)