Lenalidomide With or Without Ixazomib Citrate and Dexamethasone in Treating Patients With Residual Multiple Myeloma After Donor Stem Cell Transplant

NCT02389517 | Completed Phase 2 Results DMC

• 5 other identifiers: IRB14-0899NCI-2015-00138X1604714-0899P30CA014599
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well lenalidomide alone compared to lenalidomide, ixazomib citrate, and dexamethasone work in treating patients with multiple myeloma that remains (residual) after donor stem cell transplant. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells and may also prevent the growth of new blood vessels that are needed for cancer growth. Ixazomib citrate may stop the growth of cancer cells by interfering with proteins necessary for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide is more effective with or without ixazomib citrate and dexamethasone in treating residual multiple myeloma.

Conditions

Plasma Cell Myeloma; Residual Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With MRD Negativity

  Rate of MRD negativity after 12 months of treatment with Ixazomib in combination with lenalidomide and dexamethasone compared to MRD negativity rate after 12 months of lenalidomide alone. For the majority of patients, where MRD positivity at screening will be determined by Multi-parameter Flow Cytometry (MFC), an improvement will be defined as a conversion from MRD-positive to MRD-negative disease by MFC. Additionally, in the fraction of patients with MRD-negative disease by MFC at screening, who were MRD-positive by Next Generation Sequencing (NGS), an improvement will be defined as a conversion from MRD-positive to MRD-negative disease by NGS

  At 12 months

Secondary Outcomes (6)

• Overall Response (Number of Participants With VGPR, CR, sCR)

  At 6 months

• Duration of MRD-negative Disease

  every 28 days, up to 2 years

• Progression Free Survival

  up to 2 years

• Overall Survival

  Up to 2 years

• Number of Patients With Adverse Events

  Up to 30 days post-treatment, **up to 2 years**

Study Arms (2)

Arm I (ixazomib citrate, lenalidomide, dexamethasone)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15, lenalidomide PO QD on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22 (of courses 1-4 only).

Drug: Ixazomib Citrate; Drug: Lenalidomide; Drug: Dexamethasone

Arm II (lenalidomide)

ACTIVE COMPARATOR

Patients receive lenalidomide PO as in Arm I.

Drug: Lenalidomide

Interventions

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, proteasome inhibitor MLN9708

Arm I (ixazomib citrate, lenalidomide, dexamethasone)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, IMiD-1

Arm I (ixazomib citrate, lenalidomide, dexamethasone); Arm II (lenalidomide)

Dexamethasone DRUG

Given PO

Also known as: DM

Arm I (ixazomib citrate, lenalidomide, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Patients who completed induction treatment followed by autologous stem cell transplant as initial therapy for symptomatic myeloma as per IMWG criteria and initiated Revlimid (lenalidomide) maintenance
• Patients must have initiated lenalidomide maintenance at approximately 3 months post autologous stem transplant (preferably 70-90 but not more than 120 days)
• Patients must be receiving lenalidomide 10 mg or 15 mg and be able to tolerate dose escalation to 25 mg daily
• Patients must have received lenalidomide maintenance for 3 months (+1 month window for a maximum of 4 months lenalidomide prior to enrollment)
• No evidence of progressive disease on lenalidomide
• Any measurable residual disease at the time of screening for the study documented in at least one of the following ways:
• Serum protein electrophoresis (SPEP)/immunofixation studies (IFIX) positive disease
• Freelite only positive disease
• SPEP/IFIX - negative and Freelite- negative but MRD-positive disease is allowed
• Evidence of MRD at the time of screening for this study by multi-color flow cytometry (bone marrow procedure at screening required)
• Bone marrow specimen will be required at study entry; available deoxyribonucleic acid (DNA) sample will be used for calibration step for MRD evaluation by gene sequencing
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Bilirubin =\<1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN

You may not qualify if:

• Evidence of progressive disease on lenalidomide maintenance as per IMWG criteria
• Patients who have already started or received multi-drug consolidation regimen post-transplant expect for lenalidomide maintenance
• Diarrhea \> grade 1 in the absence of anti-diarrheals
• Central nervous system involvement
• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• History of allergy to mannitol
• Major surgery within 14 days before enrollment
• Radiotherapy within 14 days before randomization; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled cardiac conditions such as hypertension, or cardiac arrhythmias, or New York Heart Association stage III and IV congestive heart failure, or unstable angina or myocardial infarction within the past 6 months
• Rate-corrected QT interval of electrocardiograph (QTc) \> 470 msec on a 12-lead electrocardiogram (ECG) during screening
• Uncontrolled diabetes
• Acute infection requiring systemic anti-infectives, antivirals, or antifungals within two weeks prior to first dose
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450 family 3, subfamily A CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator
• Multiple Myeloma Research Foundation: collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

ixazomib; Lenalidomide; Dexamethasone

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Results Point of Contact

• Title: Andrzej Jakubowiak
• Organization: University of Chicago

ajakubowiak@medicine.bsd.uchicago.edu

855-702-8222

Study Officials

• Andrzej Jakubowiak

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: March 2, 2015
• Primary Completion: February 1, 2021
• Study Completion: January 1, 2024
• Last Updated: January 22, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

Locations

US (1)