A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma

NCT ID: NCT02076009

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 569 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-23
• Study Completion Date: 2024-11-21

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.

Detailed Description

This is a randomized (participants will be assigned by chance to study treatments), open-label (all participants and study personnel will know the identity of the study treatments), active-controlled (none of the study treatments are placebo), parallel-group (both treatment arms will run at the same time), multicenter study. In this study, daratumumab, lenalidomide, and low-dose dexamethasone (DRd) will be compared with lenalidomide and low dose dexamethasone (Rd) in participants with relapsed or refractory multiple myeloma. Participants will be randomized in a 1:1 ratio to receive either DRd or Rd. The study will include a Screening Phase, a Treatment Phase (involving treatment cycles of approximately 28 days in length), and a Follow-up Phase. The Treatment Phase will extend from the administration of the first dose of study medication until disease progression or unacceptable toxicity. Participants will also discontinue study treatment if: they become pregnant; have their dose held for more than 28 days (or if 3 consecutive planned doses of daratumumab are missed for reasons other than toxicity); or for safety reasons (for example, adverse event). The Follow-up Phase will begin at the end of treatment and will continue until death, loss to follow-up, consent withdrawal for study participation, or the final overall survival (OS) analysis, whichever occurs first. Eligible participants from Rd group who have had sponsor confirmed disease progression will be offered the option for treatment with daratumumab monotherapy (of 28 days cycle). The primary endpoint will be progression-free survival (PFS). Analysis of the primary endpoint was performed at a pre-specified point determined by PFS events with a clinical cutoff of March 7, 2016 when 169 events of death or progression had occurred. The end of study is anticipated at approximately 6 years after the last participant is randomized. Blood and urine samples will be obtained at time points during the study, together with bone marrow aspirates/biopsies and skeletal surveys. Participant safety will be assessed throughout the study.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Daratumumab + lenalidomide + dexamethasone

During each 28-day treatment cycle, participants will receive daratumumab, lenalidomide, and dexamethasone.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

Intervention Type: DRUG

Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.

Dexamethasone

Intervention Type: DRUG

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).

Lenalidomide + dexamethasone

During each 28-day treatment cycle, participants will receive lenalidomide and dexamethasone.

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.

Dexamethasone

Intervention Type: DRUG

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).

Interventions

Daratumumab

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.

Intervention Type: DRUG

Lenalidomide

Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.

Intervention Type: DRUG

Dexamethasone

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 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

Little Rock, Arkansas, United States

Gainesville, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Iowa City, Iowa, United States

Louisville, Kentucky, United States

Baton Rouge, Louisiana, United States

New Orleans, Louisiana, United States

Bethesda, Maryland, United States

Columbia, Maryland, United States

Boston, Massachusetts, United States

Rochester, Minnesota, United States

Omaha, Nebraska, United States

New Brunswick, New Jersey, United States

New York, New York, United States

Charlotte, North Carolina, United States

Eugene, Oregon, United States

Spartanburg, South Carolina, United States

Austin, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Fairfax, Virginia, United States

Camperdown, , Australia

Geelong, , Australia

Heidelberg, , Australia

Malvern, , Australia

South Brisbane, , Australia

Southport, , Australia

Anderlecht, , Belgium

Antwerp, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Kortrijk, , Belgium

Leuven, , Belgium

Liège, , Belgium

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Surrey, British Columbia, Canada

Vancouver, British Columbia, Canada

Halifax, Nova Scotia, Canada

Hamilton, Ontario, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

Copenhagen, , Denmark

Odense, , Denmark

Vejle, , Denmark

Argenteuil, , France

Caen, , France

Lille, , France

Limoges, , France

Nantes, , France

Paris, , France

Pessac, , France

Pierre-Bénite, , France

Rennes, , France

Toulouse, , France

Tours, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Bonn, , Germany

Cologne, , Germany

Hamburg, , Germany

Hamm, , Germany

Heidelberg, , Germany

Jena, , Germany

Karlsruhe, , Germany

Koblenz, , Germany

Saarbrücken, , Germany

Villingen-Schwenningen, , Germany

Athens Attica, , Greece

Haifa, , Israel

Jerusalem, , Israel

Nahariya, , Israel

Netanya, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Hitachi, , Japan

Kanazawa, , Japan

Kobe, , Japan

Kurume, , Japan

Matsuyama, , Japan

Nagoya, , Japan

Narita, , Japan

Ohgaki, , Japan

Okayama, , Japan

Osaka, , Japan

Sendai, , Japan

Shibukawa, , Japan

Shibuya City, , Japan

Tachikawa, , Japan

Tokyo, , Japan

Amsterdam, , Netherlands

Rotterdam, , Netherlands

Utrecht, , Netherlands

Zwolle, , Netherlands

Brzozów, , Poland

Chorzów, , Poland

Gdansk, , Poland

Legnica, , Poland

Lublin, , Poland

Poznan, , Poland

Słupsk, , Poland

Wroclawa, , Poland

Dzerzhinsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Petrozavodsk, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Syktyvkar, , Russia

Yekaterinburg, , Russia

Gyeonggi-do, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Badalona, , Spain

Barcelona, , Spain

La Laguna (Santa Cruz de Tenerife), , Spain

Madrid, , Spain

Pamplona, , Spain

Salamanca, , Spain

Seville, , Spain

Falun, , Sweden

Gothenburg, , Sweden

Helsingborg, , Sweden

Huddinge, , Sweden

Lund, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Changhua, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Birmingham, , United Kingdom

Leeds, , United Kingdom

London, , United Kingdom

Oxford, , United Kingdom

Southampton, , United Kingdom

Surrey, , United Kingdom

Wolverhampton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Denmark; France; Germany; Greece; Israel; Japan; Netherlands; Poland; Russia; South Korea; Spain; Sweden; Taiwan; United Kingdom

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Other Identifiers

54767414MMY3003

Identifier Type: OTHER

Identifier Source: secondary_id

2013-005525-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR103663

Identifier Type: -

Identifier Source: org_study_id