NCT02252172

Brief Summary

The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
737

participants targeted

Target at P75+ for phase_3 multiple-myeloma

Timeline
Completed

Started Feb 2015

Longer than P75 for phase_3 multiple-myeloma

Geographic Reach
12 countries

201 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 11, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 30, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

February 16, 2015

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 24, 2018

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

January 9, 2020

Completed
4.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 2, 2024

Completed
Last Updated

October 20, 2025

Status Verified

October 1, 2025

Enrollment Period

3.6 years

First QC Date

August 11, 2014

Results QC Date

September 24, 2019

Last Update Submit

October 1, 2025

Conditions

Keywords

Multiple MyelomaDaratumumabJNJ-54767414LenalidomideDexamethasone

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS)

    PFS was defined as time from date of randomization to either progressive disease (PD) or death, whichever occurred first based on computerized algorithm as per IMWG criteria. PD was defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to \[\>=\] 0.5 gram per deciliter \[g/dL\] and \>=200 milligram \[mg\]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than \[\>\]10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that could be attributed solely to Plasma cell (PC) proliferative disorder.

    From randomization (Day -3) to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years)

Secondary Outcomes (16)

  • Percentage of Participants With Complete Response (CR) or Better

    From randomization (Day -3) up to 6.6 years

  • Percentage of Participants With Very Good Partial Response (VGPR) or Better

    From randomization (Day -3) up to 6.6 years

  • Percentage of Participants With Negative Minimal Residual Disease (MRD)

    From randomization (Day -3) up to 6.6 years

  • Percentage of Participants With Stringent Complete Response (sCR)

    From randomization (Day -3) up to 6.6 years

  • Overall Response Rate (ORR)

    From randomization (Day -3) up to 6.6 years

  • +11 more secondary outcomes

Study Arms (2)

Lenalidomide and Dexamethasone (Rd)

ACTIVE COMPARATOR

Participants will receive Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

Drug: Daratumumab IVDrug: LenalidomideDrug: Dexamethasone

Daratumumab + Lenalidomide + Dexamethasone (DRd)

ACTIVE COMPARATOR

Participants will receive Daratumumab 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks, Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

Drug: LenalidomideDrug: DexamethasoneDrug: Daratumumab SC

Interventions

Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).

Also known as: JNJ-54767414
Lenalidomide and Dexamethasone (Rd)

Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.

Daratumumab + Lenalidomide + Dexamethasone (DRd)Lenalidomide and Dexamethasone (Rd)

Dexamethasone 40 mg orally or intravenously once in a week.

Daratumumab + Lenalidomide + Dexamethasone (DRd)Lenalidomide and Dexamethasone (Rd)

Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study end. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator.

Also known as: JNJ-54767414
Daratumumab + Lenalidomide + Dexamethasone (DRd)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (\>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein \[M-protein\] level \>=1.0 gram/deciliter \[g/dL\] or urine M-protein level \>=200 milligram\[mg\]/24 hours\[hrs\]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level \>=0.5 g/dL or urine M-protein level \>=200 mg/24 hrs); or (c) light chain multiple myeloma without measurable disease in serum or urine (serum immunoglobulin free light chain \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Participants who are newly diagnosed and not considered for high-dose chemotherapy due to: being age \>=65 years; or participants less than (\<) 65 years with presence of important comorbid condition(s) likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. Sponsor review and approval of participants below 65 years of age is required before randomization
  • Women of childbearing potential must commit to either abstain continuously from sexual intercourse or to use 2 methods of reliable birth control simultaneously as deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab
  • Man, who is sexually active with a woman of child-bearing potential must agree to use a latex or synthetic condom, even if he had a successful vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for 4 weeks after last dose of lenalidomide and 4 months after last dose of daratumumab

You may not qualify if:

  • Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein \<3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)
  • Participant has a diagnosis of Waldenström's disease, or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
  • Participant has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
  • Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
  • Participant has had radiation therapy within 14 days of randomization
  • Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
  • Participants with known or suspected COPD must have a FEV1 test during Screening
  • Participant is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\] or antibodies to hepatitis B surface and core antigens \[anti-HBs and anti-HBc, respectively\]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid \[RNA\] quantitation positive)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (206)

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Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Glendale, Arizona, United States

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Berkeley, California, United States

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Beverly Hills, California, United States

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El Cajon, California, United States

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Greenbrae, California, United States

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Los Angeles, California, United States

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Oceanside, California, United States

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San Diego, California, United States

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West Hills, California, United States

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Whittier, California, United States

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Denver, Colorado, United States

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Fort Collins, Colorado, United States

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Glenwood Springs, Colorado, United States

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New Haven, Connecticut, United States

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Norwalk, Connecticut, United States

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

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Boca Raton, Florida, United States

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Boynton Beach, Florida, United States

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Fort Lauderdale, Florida, United States

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Fort Myers, Florida, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Lake City, Florida, United States

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St. Petersburg, Florida, United States

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Weston, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Macon, Georgia, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Niles, Illinois, United States

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Fort Wayne, Indiana, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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Lafayette, Louisiana, United States

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Marrero, Louisiana, United States

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Shreveport, Louisiana, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Frederick, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Duluth, Minnesota, United States

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Rochester, Minnesota, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Hooksett, New Hampshire, United States

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Brick, New Jersey, United States

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Hackensack, New Jersey, United States

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Livingston, New Jersey, United States

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Plainfield, New Jersey, United States

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Summit, New Jersey, United States

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Mineola, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Asheboro, North Carolina, United States

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Charlotte, North Carolina, United States

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Pinehurst, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Canton, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Bend, Oregon, United States

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Bethlehem, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Spartanburg, South Carolina, United States

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Sioux Falls, South Dakota, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Edinburg, Texas, United States

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Fort Sam Houston, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Ogden, Utah, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Box Hill, Australia

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Fitzroy, Australia

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Footscray, Australia

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Kogarah, Australia

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Kurralta Park, Australia

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Nedlands, Australia

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New South Wales, Australia

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Woodville, Australia

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Woolloongabba, Australia

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Innsbruck, Austria

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Linz, Austria

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Salzburg, Austria

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Vienna, Austria

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Wien Wien, Austria

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Bruges, Belgium

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Brussels, Belgium

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Haine Saint Paul La Louviere, Belgium

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Leuven, Belgium

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Liège, Belgium

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Calgary, Alberta, Canada

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Nova Scotia, Nova Scotia, Canada

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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N/a N/a, Canada

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Aarhus C, Denmark

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Odense, Denmark

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Vejle, Denmark

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Amiens N/a Picardie, France

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Angers, France

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Bayonne, France

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Bretagne, France

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Caen, France

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Cergy-Pontoise, France

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Chalon-sur-Saône, France

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Clermont-Ferrand, France

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Créteil, France

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Dijon, France

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Dunkirk, France

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Grenoble, France

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La Roche-sur-Yon, France

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Le Chesnay, France

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Le Mans, France

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Lille, France

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Limoges, France

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Lyon, France

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Marseille, France

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Metz-Tessy, France

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Montivilliers, France

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Montpellier, France

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Mulhouse, France

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Nantes, France

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Nice, France

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Paris, France

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Perpignan, France

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Pessac, France

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Périgueux, France

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Poitiers, France

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Reims, France

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Rennes, France

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Rouen, France

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Saint-Brieuc, France

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Saint-Priest-en-Jarez, France

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Saint-Quentin, France

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St-Malo, France

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Strasbourg, France

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Toulouse, France

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Tours, France

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Vandœuvre-lès-Nancy, France

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Aschaffenburg, Germany

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Bad Berka, Germany

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Bonn, Germany

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Braunschweig, Germany

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Dresden, Germany

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Essen, Germany

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Frankfurt, Germany

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Hanover, Germany

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Heidelberg, Germany

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Hessen, Germany

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Kiel, Germany

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Koblenz, Germany

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Mainz, Germany

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Mannheim, Germany

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Rostock, Germany

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Schwerin, Germany

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Stuttgart, Germany

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Tübingen, Germany

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Ulm, Germany

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Villingen-Schwenningen, Germany

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Dublin, Ireland

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Galway, Ireland

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Hadera, Israel

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Haifa, Israel

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Jerusalem, Israel

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Nahariya, Israel

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Petah Tikva, Israel

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Tel Aviv, Israel

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Hilversum, Netherlands

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Hoofddorp, Netherlands

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Rotterdam, Netherlands

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Tilburg, Netherlands

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Falun, Sweden

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Gothenburg, Sweden

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Halmstad, Sweden

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Helsingborg, Sweden

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Huddinge, Sweden

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Luleå, Sweden

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Lund, Sweden

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Örebro, Sweden

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Stockholm, Sweden

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Aberdeen, United Kingdom

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Canterbury, United Kingdom

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Dundee, United Kingdom

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Leeds, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Nottingham, United Kingdom

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Oxford, United Kingdom

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Plymouth, United Kingdom

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Southampton, United Kingdom

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Truro, United Kingdom

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Wolverhampton, United Kingdom

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Related Publications (10)

  • Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, Hulin C, Orlowski RZ, Nahi H, Mollee P, Ramasamy K, Roussel M, Jaccard A, Delforge M, Karlin L, Arnulf B, Chari A, Wang G, Gupta-Werner N, Kaila S, Pei H, Matt K, Gries KS, Carson R, Borgsten F, Weisel K. Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, and Dexamethasone: MAIA Final Analysis of Patient-Reported Outcomes. Eur J Haematol. 2025 May;114(5):883-889. doi: 10.1111/ejh.14392. Epub 2025 Feb 14.

  • Moreau P, Facon T, Usmani SZ, Bahlis N, Raje N, Plesner T, Orlowski RZ, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Tiab M, Macro M, Frenzel L, Leleu X, Wang G, Pei H, Krevvata M, Carson R, Borgsten F, Kumar SK. Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study. Leukemia. 2025 Mar;39(3):710-719. doi: 10.1038/s41375-024-02506-1. Epub 2025 Jan 15.

  • Almansour SA, Alqudah MAY, Abuhelwa Z, Al-Shamsi HO, Alhuraiji A, Semreen MH, Bustanji Y, Alzoubi KH, Modi ND, Mckinnon RA, Sorich MJ, Hopkins AM, Abuhelwa AY. Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials. Ther Adv Med Oncol. 2024 Sep 2;16:17588359241275387. doi: 10.1177/17588359241275387. eCollection 2024.

  • Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, Perrot A, Weisel K, Raje N, Macro M, Frenzel L, Leleu X, Wang J, Rampelbergh RV, Uhlar CM, Vermeulen J, Duran J, Borgsten F, Usmani SZ. Plain language summary of the MAIA study of daratumumab plus lenalidomide and dexamethasone for the treatment of people with newly diagnosed multiple myeloma. Future Oncol. 2023 Apr;19(13):887-895. doi: 10.2217/fon-2023-0082. Epub 2023 May 22.

  • Mateos MV, Rigaudeau S, Basu S, Spicka I, Schots R, Wrobel T, Cook G, Beksac M, Gries KS, Kudva A, Tromp B, Van Rampelbergh R, Pei H, Wroblewski S, Carson R, Delioukina M, White D. Switching to daratumumab SC from IV is safe and preferred by patients with multiple myeloma. J Oncol Pharm Pract. 2023 Jul;29(5):1172-1177. doi: 10.1177/10781552221103551. Epub 2022 Sep 6.

  • Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Wang J, Van Rampelbergh R, Uhlar CM, Tromp B, Delioukina M, Vermeulen J, Usmani SZ. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Nov;22(11):1582-1596. doi: 10.1016/S1470-2045(21)00466-6. Epub 2021 Oct 13.

  • Cavo M, San-Miguel J, Usmani SZ, Weisel K, Dimopoulos MA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria V, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar S, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi N. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2022 Feb 10;139(6):835-844. doi: 10.1182/blood.2021011101.

  • San-Miguel J, Avet-Loiseau H, Paiva B, Kumar S, Dimopoulos MA, Facon T, Mateos MV, Touzeau C, Jakubowiak A, Usmani SZ, Cook G, Cavo M, Quach H, Ukropec J, Ramaswami P, Pei H, Qi M, Sun S, Wang J, Krevvata M, DeAngelis N, Heuck C, Van Rampelbergh R, Kudva A, Kobos R, Qi M, Bahlis NJ. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022 Jan 27;139(4):492-501. doi: 10.1182/blood.2020010439.

  • Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, Hulin C, Orlowski RZ, Nahi H, Mollee P, Ramasamy K, Roussel M, Jaccard A, Delforge M, Karlin L, Arnulf B, Chari A, He J, Ho KF, Van Rampelbergh R, Uhlar CM, Wang J, Kobos R, Gries KS, Fastenau J, Weisel K. Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial. J Clin Oncol. 2021 Jan 20;39(3):227-237. doi: 10.1200/JCO.20.01370. Epub 2020 Dec 16.

  • Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ; MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.

MeSH Terms

Conditions

Multiple Myeloma

Interventions

LenalidomideDexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Results Point of Contact

Title
Director
Organization
Janssen Research & Development, LLC

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

August 11, 2014

First Posted

September 30, 2014

Study Start

February 16, 2015

Primary Completion

September 24, 2018

Study Completion

October 2, 2024

Last Updated

October 20, 2025

Results First Posted

January 9, 2020

Record last verified: 2025-10

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