A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma
3 other identifiers
interventional
569
18 countries
145
Brief Summary
The purpose of this study is to compare the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started Jul 2014
Longer than P75 for phase_3 multiple-myeloma
145 active sites
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
February 27, 2014
CompletedFirst Posted
Study publicly available on registry
March 3, 2014
CompletedStudy Start
First participant enrolled
July 23, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 7, 2016
CompletedResults Posted
Study results publicly available
February 10, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 21, 2024
CompletedMay 1, 2025
April 1, 2025
1.6 years
February 27, 2014
December 20, 2016
April 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
PFS: duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD: defined as meeting any 1 of following criteria: Increase of greater than equal to (\>=)25 percent(%) in level of serum M-protein from lowest response value and absolute increase must be \>=0.5 gram per deciliter (g/dL); Increase of \>=25% in 24-hours(h) urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be \>=200 mg/24h; Only in participants without measurable serum and urine M-protein levels: increase of \>=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be \>10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) attributed solely to plasma cell (PC) proliferative disorder.
From randomization to either disease progression or death whichever occurs first (up to 21 months)
Secondary Outcomes (8)
Time to Disease Progression (TTP)
From randomization to disease progression (up to 21 months)
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
From randomization to disease progression (up to 21 months)
Percentage of Participants With Negative Minimal Residual Disease (MRD)
From randomization to the date of first documented evidence of PD (up to 87.5 months)
Overall Response Rate
From randomization to disease progression (up to 21 months)
Overall Survival (OS)
From randomization to date of death due to any cause (up to 87.5 months)
- +3 more secondary outcomes
Study Arms (2)
Daratumumab + lenalidomide + dexamethasone
EXPERIMENTALDuring each 28-day treatment cycle, participants will receive daratumumab, lenalidomide, and dexamethasone.
Lenalidomide + dexamethasone
ACTIVE COMPARATORDuring each 28-day treatment cycle, participants will receive lenalidomide and dexamethasone.
Interventions
Daratumumab 16mg/kg will be administered as an intravenous (IV) infusion (into the vein) as per the following schedule: once a week during treatment cycles 1 and 2; every 2 weeks during treatment cycles 3 to 6; and every 4 weeks for cycles 7 and onwards. Following amendment 8, participants receiving daratumumab IV have the option to switch to daratumumab subcutaneous (SC) 1800 mg/dose until documented progression, unacceptable toxicity, or the end of study on Day 1 of any cycle, at the discretion of the investigator.
Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.
Dexamethasone (or equivalent in accordance with local standards) will be administered as a total dose of 40 mg weekly (or 20 mg weekly for participants \> 75 years old or with a body mass index \< 18.5).
Eligibility Criteria
You may qualify if:
- Must have documented multiple myeloma and measurable disease
- Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
- Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
- Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a "wash-out period" defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy
You may not qualify if:
- Has received any of the following therapies: daratumumab or other anti-CD38 therapies
- Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment
- Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
- Has received autologous stem cell transplantation within 12 weeks before the date of randomization, or previously received an allogenic stem cell transplant (regardless of timing), or planning to undergo a stem cell transplant prior to progression of disease
- History of malignancy (other than multiple myeloma) within 5 years before the first dose of daratumumab monotherapy (exceptions are squamous and basal cell carcinomas of the skin and 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 5 years)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (145)
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Little Rock, Arkansas, United States
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Gainesville, Florida, United States
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West Palm Beach, Florida, United States
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Atlanta, Georgia, United States
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Chicago, Illinois, United States
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Iowa City, Iowa, United States
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Louisville, Kentucky, United States
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Baton Rouge, Louisiana, United States
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New Orleans, Louisiana, United States
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Bethesda, Maryland, United States
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Columbia, Maryland, United States
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Boston, Massachusetts, United States
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Rochester, Minnesota, United States
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Omaha, Nebraska, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
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Charlotte, North Carolina, United States
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Eugene, Oregon, United States
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Spartanburg, South Carolina, United States
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Austin, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Fairfax, Virginia, United States
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Camperdown, Australia
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Geelong, Australia
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Heidelberg, Australia
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Malvern, Australia
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South Brisbane, Australia
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Southport, Australia
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Anderlecht, Belgium
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Antwerp, Belgium
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Edegem, Belgium
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Ghent, Belgium
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Kortrijk, Belgium
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Leuven, Belgium
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Liège, Belgium
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Surrey, British Columbia, Canada
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Vancouver, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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Hamilton, Ontario, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Copenhagen, Denmark
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Odense, Denmark
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Vejle, Denmark
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Argenteuil, France
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Caen, France
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Lille, France
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Limoges, France
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Nantes, France
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Paris, France
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Pessac, France
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Pierre-Bénite, France
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Rennes, 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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Berlin, Germany
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Bonn, Germany
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Cologne, Germany
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Hamburg, Germany
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Hamm, Germany
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Heidelberg, Germany
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Jena, Germany
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Karlsruhe, Germany
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Koblenz, Germany
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Saarbrücken, Germany
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Villingen-Schwenningen, Germany
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Athens Attica, Greece
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Haifa, Israel
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Jerusalem, Israel
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Nahariya, Israel
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Netanya, Israel
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Petah Tikva, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Hitachi, Japan
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Kanazawa, Japan
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Kobe, Japan
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Kurume, Japan
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Matsuyama, Japan
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Nagoya, Japan
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Narita, Japan
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Ohgaki, Japan
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Okayama, Japan
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Osaka, Japan
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Sendai, Japan
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Shibukawa, Japan
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Shibuya City, Japan
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Tachikawa, Japan
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Tokyo, Japan
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Amsterdam, Netherlands
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Rotterdam, Netherlands
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Utrecht, Netherlands
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Zwolle, Netherlands
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Brzozów, Poland
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Chorzów, Poland
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Gdansk, Poland
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Legnica, Poland
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Lublin, Poland
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Poznan, Poland
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Słupsk, Poland
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Wroclawa, Poland
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Dzerzhinsk, Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Petrozavodsk, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Samara, Russia
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Syktyvkar, Russia
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Yekaterinburg, Russia
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Gyeonggi-do, South Korea
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Incheon, South Korea
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Seoul, South Korea
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Badalona, Spain
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Barcelona, Spain
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La Laguna (Santa Cruz de Tenerife), Spain
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Madrid, Spain
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Pamplona, Spain
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Salamanca, Spain
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Seville, Spain
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Falun, Sweden
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Gothenburg, Sweden
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Helsingborg, Sweden
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Huddinge, Sweden
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Lund, Sweden
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Stockholm, Sweden
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Uppsala, Sweden
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Changhua, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Birmingham, United Kingdom
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Leeds, United Kingdom
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London, United Kingdom
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Oxford, United Kingdom
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Southampton, United Kingdom
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Surrey, United Kingdom
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Wolverhampton, United Kingdom
Related Publications (8)
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.
PMID: 39229471DERIVEDSpencer A, Moreau P, Mateos MV, Goldschmidt H, Suzuki K, Levin MD, Sonneveld P, Orlowski RZ, Yoon SS, Usmani SZ, Weisel K, Reece D, Ahmadi T, Pei H, Mayo WG, Gai X, Carey J, Bartlett JB, Carson R, Dimopoulos MA. Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX. Blood Adv. 2024 Jan 23;8(2):388-398. doi: 10.1182/bloodadvances.2023010579.
PMID: 38048391DERIVEDDimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Ahmadi T, Qin X, Garvin Mayo W, Gai X, Carey J, Carson R, Moreau P. Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2023 Mar 10;41(8):1590-1599. doi: 10.1200/JCO.22.00940. Epub 2023 Jan 4.
PMID: 36599114DERIVEDCavo 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.
PMID: 34289038DERIVEDPlesner T, Dimopoulos MA, Oriol A, San-Miguel J, Bahlis NJ, Rabin N, Suzuki K, Yoon SS, Ben-Yehuda D, Cook G, Goldschmidt H, Grosicki S, Qin X, Fastenau J, Garvin W, Carson R, Renaud T, Gries KS. Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial. Br J Haematol. 2021 Jul;194(1):132-139. doi: 10.1111/bjh.17435. Epub 2021 Apr 6.
PMID: 33822368DERIVEDAvet-Loiseau H, San-Miguel J, Casneuf T, Iida S, Lonial S, Usmani SZ, Spencer A, Moreau P, Plesner T, Weisel K, Ukropec J, Chiu C, Trivedi S, Amin H, Krevvata M, Ramaswami P, Qin X, Qi M, Sun S, Qi M, Kobos R, Bahlis NJ. Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR. J Clin Oncol. 2021 Apr 1;39(10):1139-1149. doi: 10.1200/JCO.20.01814. Epub 2021 Jan 29.
PMID: 33513030DERIVEDMateos MV, Spencer A, Nooka AK, Pour L, Weisel K, Cavo M, Laubach JP, Cook G, Iida S, Benboubker L, Usmani SZ, Yoon SS, Bahlis NJ, Chiu C, Ukropec J, Schecter JM, Qin X, O'Rourke L, Dimopoulos MA. Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica. 2020 Jan 31;105(2):468-477. doi: 10.3324/haematol.2019.217448. Print 2020.
PMID: 31221782DERIVEDDimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.
PMID: 27705267DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Director, Clinical Research
- Organization
- Janssen R&D US
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
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
February 27, 2014
First Posted
March 3, 2014
Study Start
July 23, 2014
Primary Completion
March 7, 2016
Study Completion
November 21, 2024
Last Updated
May 1, 2025
Results First Posted
February 10, 2017
Record last verified: 2025-04