Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT02136134

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 498 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-15
• Study Completion Date: 2024-01-10

Brief Summary

The purpose of this study is to assess the effects of administration of daratumumab when combined with VELCADE (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma.

Detailed Description

This is an open-label (physicians and participants know the identity of the assigned treatment), randomized (the study medication is assigned by chance), multicenter, active-controlled study comparing daratumumab, VELCADE, and dexamethasone (DVd) with VELCADE and dexamethasone (Vd) in participants with relapsed or refractory multiple myeloma. Approximately 480 participants will be randomly assigned in a 1:1 ratio to receive either DVd or Vd. Randomization will be stratified by International Staging System (ISS), number of prior treatment programs (1 vs. 2 or 3 vs. >3), and prior VELCADE treatment ("no" vs. "yes"). Within each stratum, participants will be randomized to one of the treatment groups.The study will consist of a Screening Phase, a Treatment Phase, and a Follow-up Phase. Participants will be treated until disease progression, unacceptable toxicity, or other reasons to discontinue the study.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Daratumumab+VELCADE+dexamethasone

Daratumumab, VELCADE and dexamethasone

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

Daratumumab will be administered as an IV infusion or 16 mg/kg weekly for the first 3 cycles, on Day 1 of Cycles 4-9, and then every 4 weeks thereafter. As per protocol amendment-6 participants receiving treatment with daratumumab IV will have the option to switch to daratumumab SC 1800 mg on Day 1 of any cycle, at the discretion of the investigator.

VELCADE (Bortezomib)

Intervention Type: DRUG

VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.

VELCADE+dexamethasone

VELCADE and dexamethasone.

Group Type: ACTIVE_COMPARATOR

VELCADE (Bortezomib)

Intervention Type: DRUG

VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.

Interventions

Daratumumab

Daratumumab will be administered as an IV infusion or 16 mg/kg weekly for the first 3 cycles, on Day 1 of Cycles 4-9, and then every 4 weeks thereafter. As per protocol amendment-6 participants receiving treatment with daratumumab IV will have the option to switch to daratumumab SC 1800 mg on Day 1 of any cycle, at the discretion of the investigator.

Intervention Type: DRUG

VELCADE (Bortezomib)

VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.

Intervention Type: DRUG

Other Intervention Names

VELCADE

Eligibility Criteria

Inclusion Criteria

• Must have had documented multiple myeloma
• Must have received at least 1 prior line of therapy for multiple myeloma
• Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
• Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
• Must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past

Exclusion Criteria

• Has received daratumumab or other anti-CD38 therapies previously
• Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
• Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
• Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day [mg/day] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
• Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
• Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures

• 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

Birmingham, Alabama, United States

Los Angeles, California, United States

Stamford, Connecticut, United States

Jacksonville, Florida, United States

Atlanta, Georgia, United States

Niles, Illinois, United States

Topeka, Kansas, United States

Westwood, Kansas, United States

Marrero, Louisiana, United States

Boston, Massachusetts, United States

Lansing, Michigan, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Providence, Rhode Island, United States

Seattle, Washington, United States

Adelaide, , Australia

Concord, , Australia

Fitzroy, , Australia

Hobart, , Australia

Melbourne, , Australia

Nedlands, , Australia

Woodville South, , Australia

Barretos, , Brazil

Porto Alegre, , Brazil

Salvador, , Brazil

São Paulo, , Brazil

Brno, , Czechia

Hradec Králové, , Czechia

Ostrava-Poruba, , Czechia

Prague, , Czechia

Bamberg, , Germany

Berlin, , Germany

Düsseldorf, , Germany

Freiburg im Breisgau, , Germany

Göttingen, , Germany

Hamburg, , Germany

Mainz, , Germany

München, , Germany

Stuttgart, , Germany

Tübingen, , Germany

Ulm, , Germany

Würzburg, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Pécs, , Hungary

Veszprém, , Hungary

Huixquilucan, , Mexico

Monterrey, , Mexico

Alkmaar, , Netherlands

Amersfoort, , Netherlands

Dordrecht, , Netherlands

Groningen, , Netherlands

Leiden, , Netherlands

Maastricht, , Netherlands

Nijmegen, , Netherlands

The Hague, , Netherlands

Chorzów, , Poland

Katowice, , Poland

Krakow, , Poland

Poznan, , Poland

Warsaw, , Poland

Krasnodar, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Penza, , Russia

Pyatigorsk, , Russia

Ryazan, , Russia

Samara, , Russia

Sochi, , Russia

Syktyvkar, , Russia

Busan, , South Korea

Hwasun, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Ulsan, , South Korea

Madrid, , Spain

Salamanca, , Spain

San Sebastián de los Reyes, , Spain

Toledo, , Spain

Valencia, , Spain

Linköping, , Sweden

Luleå, , Sweden

Lund, , Sweden

Örebro, , Sweden

Sundsvall, , Sweden

Umeå, , Sweden

Uppsala, , Sweden

Västerås, , Sweden

Ankara, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Kayseri, , Turkey (Türkiye)

Kocaeli, , Turkey (Türkiye)

Malatya, , Turkey (Türkiye)

Cherkasy, , Ukraine

Dnipro, , Ukraine

Ivano-Frankivsk, , Ukraine

Kiev, , Ukraine

Lviv, , Ukraine

Poltava, , Ukraine

Vinnitsa, , Ukraine

Zaporizhzhya, , Ukraine

Countries

United States; Australia; Brazil; Czechia; Germany; Hungary; Mexico; Netherlands; Poland; Russia; South Korea; Spain; Sweden; Turkey (Türkiye); Ukraine

References

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Other Identifiers

2014-000255-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54767414MMY3004

Identifier Type: OTHER

Identifier Source: secondary_id

CR103995

Identifier Type: -

Identifier Source: org_study_id

NCT01620879

Identifier Type: -

Identifier Source: nct_alias