A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant

NCT ID: NCT03901963

Last Updated: 2025-11-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2026-05-29

Brief Summary

The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD) negativity following the addition of daratumumab to lenalidomide relative to lenalidomide alone, when administered as maintenance treatment to anti-cluster of differentiation 38 (CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD positive as determined by next generation sequencing (NGS) at screening, following high-dose therapy (HDT) and autologous stem cell transplant (ASCT).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daratumumab + Lenalidomide

Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

Daratumumab 1800 mg will be administered by SC injection weekly during Cycles 1 and 2, every 2 weeks during Cycles 3 through 6, and every 4 weeks from Cycle 7 onward until confirmed progressive disease (PD), unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles.

Lenalidomide

Intervention Type: DRUG

Lenalidomide 10 mg will be administered orally from Day 1 to Day 28 (continuously) of each 28-day cycle until confirmed PD, unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.

Lenalidomide

Participants will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

Lenalidomide 10 mg will be administered orally from Day 1 to Day 28 (continuously) of each 28-day cycle until confirmed PD, unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.

Interventions

Daratumumab

Daratumumab 1800 mg will be administered by SC injection weekly during Cycles 1 and 2, every 2 weeks during Cycles 3 through 6, and every 4 weeks from Cycle 7 onward until confirmed progressive disease (PD), unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles.

Intervention Type: DRUG

Lenalidomide

Lenalidomide 10 mg will be administered orally from Day 1 to Day 28 (continuously) of each 28-day cycle until confirmed PD, unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.

Intervention Type: DRUG

Other Intervention Names

DARZALEX

Eligibility Criteria

Inclusion Criteria

• Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of induction therapy, have received high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) within 12 months of the start of induction therapy, and be within 6 months of ASCT on the date of randomization
• Must have a very good partial response (VGPR) or better response assessed per International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
• Must have archived bone marrow samples collected before induction treatment (that is, at diagnosis) or before transplant (for example, at the end of induction) or have existing results on the index multiple myeloma clone based on Adaptive Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD) assay. Archived bone marrow samples will be used for calibration of myeloma clonal cells to facilitate assessment of primary end point by NGS. If an existing result on index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay, as part of institutional procedures, an archived bone marrow sample is not required as long as Adaptive Biotechnologies is able to retrieve historical results on the index myeloma clone form the clinical database. Any one of the following archived samples are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube, frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment: (i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear; (iii) Please note, bone marrow core sections are not acceptable samples for analysis; (iv) In exceptional circumstances when index myeloma clone cannot be identified from the archived bone marrow sample, a post-transplant sample can be used to identify myeloma clone with permission from the sponsor
• Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS based MRD assay)
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

Exclusion Criteria

• A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the participant has no evidence of disease before the of date of randomization. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
• Must not have progressed on multiple myeloma (MM) therapy at any time prior to screening
• Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management, or (c) Plasmapheresis within 28 days of randomization
• Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma
• Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
• Have known moderate or severe persistent asthma within the past 2 years or current uncontrolled asthma of any classification
• Have any of the following: (a) Known history of seropositivity for human immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive), except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

Arizona Oncology Associates, PC - HAL

Glendale, Arizona, United States

Cancer Treatment Center of America Phoenix

Goodyear, Arizona, United States

University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center

La Jolla, California, United States

UCLA David Geffen School of Medicine

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

University of Colorado Health

Fort Collins, Colorado, United States

Yale University Medical Center

New Haven, Connecticut, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Cancer Specialists of North Florida

Jacksonville, Florida, United States

University of Miami Sylvester Cancer Center

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

University Cancer And Blood Center LLC

Athens, Georgia, United States

Illinois Cancer Specialists

Niles, Illinois, United States

Cancer Treatment Centers of America

Zion, Illinois, United States

Fort Wayne Medical Oncology and Hematology American Oncology Partners

Fort Wayne, Indiana, United States

Franciscan Health

Indianapolis, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Cancer Institute

Detroit, Michigan, United States

Cancer And Hematology Centers of Western Michigan PC

Grand Rapids, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

HCA MidAmerica Division Inc Research Medical Center

Kansas City, Missouri, United States

Summit Medical Group/MD Anderson Cancer Center

Florham Park, New Jersey, United States

Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ)

New Brunswick, New Jersey, United States

New York Oncology Hematology

Albany, New York, United States

Northwell Health

Lake Success, New York, United States

NYU Winthrop

Mineola, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Einstein Center for Cancer Care

The Bronx, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, United States

Novant Health

Charlotte, North Carolina, United States

Novant Oncology Research Institute

Winston-Salem, North Carolina, United States

Wake Forest Health Sciences

Winston-Salem, North Carolina, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Northwest Cancer Specialists PC

Portland, Oregon, United States

Oregon Health And Science University

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

West Penn Hospital

Pittsburgh, Pennsylvania, United States

University Of Pittsburgh Medical Center UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Reading Hospital/McGlinn Cancer Institute

West Reading, Pennsylvania, United States

Greenville Health System Cancer Institute

Greenville, South Carolina, United States

Spartanburg Regional Health Services

Spartanburg, South Carolina, United States

Tennessee Oncology

Chattanooga, Tennessee, United States

Baptist Cancer Center

Memphis, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Texas Oncology-Central South

Austin, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Texas Oncology P A

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Mays Cancer Center (UT Health San Antonio)

San Antonio, Texas, United States

Texas Oncology P A

Tyler, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic

Charlottesville, Virginia, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

VA Puget Sound Healthcare System

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Cancer Care Northwest

Spokane, Washington, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

CHU de Quebec Universite Laval Hopital de l Enfant Jesus

Québec, Quebec, Canada

Countries

United States; Canada

References

Badros A, Foster L, Anderson LD Jr, Chaulagain CP, Pettijohn E, Cowan AJ, Costello C, Larson S, Sborov DW, Shain KH, Silbermann R, Shah N, Chung A, Krevvata M, Pei H, Patel S, Khare V, Cortoos A, Carson R, Lin TS, Voorhees P. Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study. Blood. 2025 Jan 16;145(3):300-310. doi: 10.1182/blood.2024025746.

Reference Type: DERIVED

PMID: 39331724 (View on PubMed)

Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.

Reference Type: DERIVED

PMID: 35985959 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54767414MMY3021

Identifier Type: OTHER

Identifier Source: secondary_id

CR108599

Identifier Type: -

Identifier Source: org_study_id