A Phase II Trial If Nivolumab, Lenalidomide and Dexamethasone in High Risk Smoldering Myeloma
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|ClinicalTrials.gov Identifier: NCT02903381|
Recruitment Status : Suspended (FDA Partial Clinical Hold)
First Posted : September 16, 2016
Last Update Posted : July 21, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Smoldering Multiple Myeloma||Drug: Nivolumab Drug: Lenalidomide Drug: Dexamethasone||Phase 2|
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;
- 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.
- "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.
- 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.
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||February 2024|
Experimental: Nivolumab, Lenalidomide, Dexamethasone
Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and
Other Name: Opdivo®
Oral, predetermined dosage, Days 1-21 of cycle 1-12
Other Name: Revlimid
Oral, Days 1, 8, 15 of cycle 1-6
- 2 Year Progression Free Rate [ Time Frame: 2 Year ]The primary endpoint will be the 2-year progression-free rate and will be analyzed using binomial probability and corresponding 90% confidence interval. All patients who have received one dose of study treatment will be included for the TTP analysis, including those who die or are lost to follow-up within 2 years.
- Objective Response Rate [ Time Frame: 2 Years ]The objective response rate (partial response or better according to the modified International Myeloma Working Group (IMWG) criteria) and the proportion of patients with a Minimal Residual Disease (MRD), Complete Response (CR), Partial Response (PR) or Minimal Response (MR) will be reported with 90% exact binominal confidence interval (CI).
- Time to Progression Rate [ Time Frame: Baseline until documented progression ]Time to progression (TTP) is defined as the time from protocol therapy initiation until documented progression, censored at date last known progression-free for those who have not progressed, up to 48 months post initiation of therapy.
- Duration of Response Rate [ Time Frame: 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 48 months post initiation of therapy. ]Kaplan-Meier method
- Progression Free Survival (PFS) Rate [ Time Frame: Baseline to e disease progression or death from any cause, censored at date last known progression free for those who have not progressed or died, up to 48 months post initiation of therapy. ]Kaplan-Meier method
- Overall Survival Rate [ Time Frame: Baseline to death or date last known alive, up to 48 months post initiation of therapy. ]Kaplan-Meier method
- Progression Free Survival Rate-Without cyclophosphamide [ Time Frame: 2 Years ]It is expected that approximately 20% of the patients will receive cyclophosphamide (CTX) for mobilization and this may influence the PFS. Therefore, in a secondary analysis the 2 year PFS rate will be evaluated among those patients who did not receive CTX.
- Number of Participants with Adverse Events [ Time Frame: Baseline to 2 Years ]For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903381
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Irene M. Ghobrial, MD||Dana-Farber Cancer Institute|