Trial of Combination of Ixazomib and Lenalidomide and Dexamethasone in Smoldering Multiple Myeloma

NCT02916771 | Completed Phase 2 Results DMC

• 1 other identifier: 16-313
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating a new drug called "ixazomib" as a possible treatment for Smoldering Multiple Myeloma.

Conditions

Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Proportion Of High Risk SMM Patients Who Are Progression Free 2 Years After Receiving IRD Combination Therapy

  The proportion of patients who achieve progression free at 2 years will be compared to the rate published for the high risk SMM. By the Mayo Clinic model for risk factors, the median time to progression for patients with high risk SMM was only 1.9 years. Therefore, we assume that, a 2-years progression-free rate of 50% will not be considered promising and a true progression free rate of 75% or higher will be considered promising.

  2 years

Secondary Outcomes (5)

• Progression Free Survival

  Time from protocol therapy initiation to the disease progression or death from any cause, censored at date last known progression free for those who have not progressed or died, or up to 60 months post initiation of therapy

• Time To Progression

  The time from protocol therapy initiation until documented progression, censored at date last known progression-free for those who have not progressed or up to 60 months post initiation of therapy

• Duration of Response

  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, or up to 60 months post initiation of therapy

• Objective Response Rate

  2 years

• Overall Survival

  Time from protocol therapy initiation to death or date last known alive, or up to 60 months post initiation of treatment

Study Arms (1)

Ixazomib

EXPERIMENTAL

* Cycles 1-9 * Ixazomib is administered orally on days 1, 8, 15 on a 28 days cycle * Lenalidomide is administered orally on days 1-21 on a 28 days cycle * Dexamethasone is administered orally on days 1, 8, 15, 22 on a 28 days cycle * Cycle 10-24 * Ixazomib is administered orally on days 1, 8, 15 on a 28 days cycle * Lenalidomide is administered orally on days 1-21 on a 28 days cycle * Supportive measures consistent with optimal patient care may be given throughout the study

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Oral, proteasome inhibitor

Also known as: Ninlaro

Ixazomib

Lenalidomide DRUG

Oral, immunomodulatory agent

Also known as: Revlimid

Ixazomib

Dexamethasone DRUG

Oral, steroid

Also known as: Decadron

Ixazomib

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%
• 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
• MRI with two or more focal lesion that is 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 radiation therapy to a solitary plasmacytoma is allowed.
• 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.
• 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 allergic reactions attributed to compounds of similar chemical or biologic composition to ixazomib or lenalidomide.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Celgene: collaborator
• Takeda: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Nadeem O, Aranha MP, Redd R, Timonian M, Magidson S, Lightbody ED, Alberge JB, Bertamini L, Dutta AK, El-Khoury H, Bustoros M, Laubach JP, Bianchi G, O'Donnell E, Wu T, Tsuji J, Anderson KC, Getz G, Trippa L, Richardson PG, Sklavenitis-Pistofidis R, Ghobrial IM. Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial. Nat Commun. 2025 Jan 3;16(1):358. doi: 10.1038/s41467-024-55308-5.

  PMID: 39753553 DERIVED

• Nadeem O, Aranha MP, Redd R, Timonian M, Magidson S, Lightbody ED, Alberge JB, Bertamini L, Dutta AK, El-Khoury H, Bustoros M, Laubach JP, Bianchi G, O'Donnell E, Wu T, Tsuji J, Anderson K, Getz G, Trippa L, Richardson PG, Sklavenitis-Pistofidis R, Ghobrial IM. Long-Term Follow-Up Defines the Population That Benefits from Early Interception in a High-Risk Smoldering Multiple Myeloma Clinical Trial Using the Combination of Ixazomib, Lenalidomide, and Dexamethasone. medRxiv [Preprint]. 2024 Apr 19:2024.04.19.24306082. doi: 10.1101/2024.04.19.24306082.

  PMID: 38699307 DERIVED

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

ixazomib; 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)

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: No
• 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: Irene M. Ghobrial, MD

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: September 27, 2016
• Study Start: October 1, 2016
• Primary Completion: January 8, 2025
• Study Completion: January 8, 2025
• Last Updated: August 11, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)