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

NCT03901963 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: CR10859954767414MMY3021
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 73

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Had Minimal Residual Disease (MRD) Conversion From Baseline to 12 Months After Start of Maintenance Treatment as Determined by Next Generation Sequencing (NGS)

  Percentage of participants who achieved MRD negative (MRD conversion) status from baseline to 12 months after maintenance treatment was defined as percentage of participants who were MRD positive at baseline (randomization) and achieved MRD negative status (at 10\^-5) during the time period from randomization to 12 months plus 2 months window, but prior to progressive disease (PD) and subsequent anti-myeloma therapy.

  From randomization up to 12 months

Secondary Outcomes (10)

• Progression-free Survival (PFS)

  From randomization to either disease progression or death (up to 7.1 years)

• Percentage of Participants Who Achieved Overall MRD (at 10^-5) Negativity Conversion From Baseline to End of Study Treatment Period

  From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years)

• Percentage of Participants Who Achieved Durable (Greater Than or Equal to [>=] 12 Months) MRD Negative Status (10^-5)

  From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years)

• Response Rates by International Myeloma Working Group (IMWG) 2016 Criteria

  From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years)

• Overall Survival (OS)

  From randomization up to 7.1 years

Study Arms (2)

Daratumumab + Lenalidomide

EXPERIMENTAL

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.

Drug: Daratumumab; Drug: Lenalidomide

Lenalidomide

ACTIVE COMPARATOR

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

Drug: Lenalidomide

Interventions

Daratumumab 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.

Also known as: DARZALEX

Daratumumab + Lenalidomide

Lenalidomide 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.

Daratumumab + Lenalidomide; Lenalidomide

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (73)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Oncology Associates, PC - HAL

Glendale, Arizona, 85308, United States

Location

Cancer Treatment Center of America Phoenix

Goodyear, Arizona, 85338, United States

Location

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

La Jolla, California, 92093, United States

Location

UCLA David Geffen School of Medicine

Los Angeles, California, 90095, 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

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

University of Colorado Health

Fort Collins, Colorado, 80528, United States

Location

Yale University Medical Center

New Haven, Connecticut, 06510, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

University of Miami Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

University Cancer And Blood Center LLC

Athens, Georgia, 30607, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Cancer Treatment Centers of America

Zion, Illinois, 60099, United States

Location

Fort Wayne Medical Oncology and Hematology American Oncology Partners

Fort Wayne, Indiana, 46804, United States

Location

Franciscan Health

Indianapolis, Indiana, 46237-8601, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66160, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer - Detroit Brigitte Harris Cancer Pavilion

Detroit, Michigan, 48202, United States

Location

Cancer And Hematology Centers of Western Michigan PC

Grand Rapids, Michigan, 49503, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

HCA MidAmerica Division Inc Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Summit Medical Group/MD Anderson Cancer Center

Florham Park, New Jersey, 07932, United States

Location

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

New Brunswick, New Jersey, 08901-1914, United States

Location

New York Oncology Hematology

Albany, New York, 12206, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

NYU Winthrop

Mineola, New York, 11501, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10467, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7305, United States

Location

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, 28204, United States

Location

Novant Health Charlotte

Charlotte, North Carolina, 28204, United States

Location

Novant Health

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45236, United States

Location

Northwest Cancer Specialists PC

Portland, Oregon, 97227, United States

Location

Oregon Health And Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107-4215, United States

Location

Temple University Hospital Jeanes Campus

Philadelphia, Pennsylvania, 19111, United States

Location

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

University Of Pittsburgh Medical Center UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Reading Hospital/McGlinn Cancer Institute

West Reading, Pennsylvania, 19611, United States

Location

Greenville Health System Cancer Institute

Greenville, South Carolina, 29615-4816, United States

Location

Spartanburg Regional Health Services

Spartanburg, South Carolina, 29303, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Central South

Austin, Texas, 78745, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Texas Oncology P A 1

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Mays Cancer Center (UT Health San Antonio)

San Antonio, Texas, 78229, United States

Location

Texas Oncology P A

Tyler, Texas, 75702, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

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

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

VA Puget Sound Healthcare System

Seattle, Washington, 98108, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Cancer Care Northwest

Spokane, Washington, 99216, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 1X6, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

CHU de Quebec Universite Laval Hopital de l Enfant Jesus

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (2)

• 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.

  PMID: 39331724 DERIVED

• 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.

  PMID: 35985959 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide

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

Results Point of Contact

• Title: Director Clinical Research Scientist
• Organization: Janssen Research & Development

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 3, 2019
• Study Start: April 26, 2019
• Primary Completion: April 4, 2024
• Study Completion (Estimated): May 29, 2026
• Last Updated: April 13, 2026
• Results First Posted: April 20, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (70); CA (3)