Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Lenalidomide and Low Dose Dexamethasone in Patients With High-Risk Smoldering Multiple Myeloma
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- 2 Year Progression Free Percent
Overview
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.
Detailed Description
-
This research study is a Phase II clinical trial, which tests the effectiveness of an investigational drug(s). The investigational drugs used in this research study are;
-
nivolumab
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lenalidomide
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dexamethasone.
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Preliminary experience suggests that the combination of lenalidomide and dexamethasone may prevent or postpone smoldering multiple myeloma (SMM) from becoming active multiple myeloma. The purpose of this research study is to determine if the addition of nivolumab may improve the rate of prevention in combination with lenalidomide and dexamethasone.
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"Investigational" means that the FDA (the U.S. Food and Drug Administration) has not approved the combination of nivolumab, lenalidomide and dexamethasone as a treatment regimen.
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Lenalidomide is an immunomodulatory drug derived from thalidomide. Lenalidomide works by stopping blood flow to your cancer cells and signaling your cancer cells to die off. The FDA has approved lenalidomide for the treatment of many types of cancer including multiple myeloma, and myelodysplastic syndromes.
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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.
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Nivolumab is approved by the FDA for some lung cancers, some skin cancers, some kidney cancers, and Hodgkin lymphoma. It is currently being evaluated for use in the treatment of several other types of cancers. Nivolumab may kill or stop cancer cells from growing by blocking a signal in the cells allowing the immune system to fight the cancer. This drug is a human monoclonal antibody, which is a molecule that is made in a laboratory that is designed to act identically to cells in the immune system.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
- •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
Exclusion Criteria
- •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%
- •Serum involved/uninvolved FLC ratio ≥100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice (light chain smoldering myeloma as described in section 2.4 is not an exclusion criteria).
- •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
- •Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonate is allowed. Prior therapy for smoldering myeloma MM may not be an exclusion criterion, discussion with Principal Investigator must occur before enrolling patients with prior treatments. Prior radiation therapy to a solitary plasmacytoma is allowed.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Arms & Interventions
Nivolumab, Lenalidomide, Dexamethasone
- 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.
Intervention: Nivolumab (Drug)
Nivolumab, Lenalidomide, Dexamethasone
- 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.
Intervention: Lenalidomide (Drug)
Nivolumab, Lenalidomide, Dexamethasone
- 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.
Intervention: Dexamethasone (Drug)
Outcomes
Primary Outcomes
2 Year Progression Free Percent
Time Frame: 2 Year
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.
Secondary Outcomes
- Overall Survival Probability at 2-years(Baseline to death or date last known alive, up to 24 months post initiation of therapy.)
- Progression Free Survival Rate-Without Cyclophosphamide(2 Years)
- Number of Participants With Adverse Events(Baseline to 2 Years)
- 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.)
Investigators
Irene Ghobrial, MD
Prinicipal Investigator
Dana-Farber Cancer Institute