Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

NCT02253316 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 201411060
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Autologous Stem Cell Transplantation; Ixazomib; Lenalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Improvement in Minimal Residual Disease (MRD)

  For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.

  After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

Secondary Outcomes (14)

• MRD-negative Rate After ASCT

  Prior to beginning consolidation treatment (Day -28 to Day 0)

• Toxicity of IRD Consolidation

  After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

• Response Rate of IRD Consolidation

  After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

• Progression-free Survival of IRD Consolidation

  Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

• Overall Survival of IRD Consolidation

  Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

Study Arms (3)

Consolidation: Ixazomib, Lenalidomide, & Dexamethasone

EXPERIMENTAL

Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, \& dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.

Biological: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Maintenance Arm 1: Ixazomib

EXPERIMENTAL

Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.

Biological: Ixazomib

Maintenance Arm 2: Lenalidomide

EXPERIMENTAL

Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.

Drug: Lenalidomide

Interventions

Ixazomib BIOLOGICAL

Also known as: [14C]-ixazomib, [14C]-MLN9708

Consolidation: Ixazomib, Lenalidomide, & Dexamethasone; Maintenance Arm 1: Ixazomib

Lenalidomide DRUG

Also known as: Revlimid

Consolidation: Ixazomib, Lenalidomide, & Dexamethasone; Maintenance Arm 2: Lenalidomide

Dexamethasone DRUG

Also known as: Aeroseb-Dex, Alba-Dex, Decaderm, Decadrol, Decadron, Decasone R.p., Decaspray, Deenar, Deronil, Dex-4, Dexace, Dexameth, Dezone, Gammacorten, Hexadrol, Maxidex, Sk-Dexamethasone

Consolidation: Ixazomib, Lenalidomide, & Dexamethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 18 and 70 years of age (inclusive) at time of enrollment
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
• Confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma with secondary amyloidosis are eligible.)
• Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) \>= 1,000 mm\^3 Platelet count \>= 75,000/mm\^3; platelet transfusions to help patient meet eligibility criteria are not allowed within 7 days before study enrollment Total bilirubin \<= 1.5 x upper limit of normal range (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=3 x ULN Calculated creatinine clearance \>= 30 mL/min
• Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS program material. This is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing.
• Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• All study participants must be registered into the mandatory Revlimind REMS program and be willing to comply with its requirements. Per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program.

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Tandem autologous transplantation
• History of plasma cell leukemia or MM CNS involvement
• Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until Day +28 post-transplant through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Prior organ transplant requiring immunosuppressive therapy
• Active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib
• Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)
• Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial infarction within the previous six months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease
• Grade \>= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period
• Major surgery within 14 days prior to enrollment
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to enrollment
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to enrollment and throughout the duration of this trial

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Multiple Myeloma Research Consortium: collaborator

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 62864, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide; Dexamethasone; Calcium Dobesilate; Glucose

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)

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; Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Ravi Vij, M.D.
• Organization: Washington University School of Medicine

rvij@wustl.edu

314-454-8323

Study Officials

• Ravi Vij, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: October 1, 2014
• Study Start: January 20, 2015
• Primary Completion: February 5, 2020
• Study Completion (Estimated): August 31, 2026
• Last Updated: November 10, 2025
• Results First Posted: September 23, 2021

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)