Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma

ClinicalTrials.gov processed this data on March 11, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED - HAS RESULTS
 (See Contacts and Locations)
Verified March 2024 by Janssen Research & Development, LLC

Sponsor

Janssen Research & Development, LLC

Information Provided by (Responsible Party)

Janssen Research & Development, LLC

Clinicaltrials.gov Identifier

NCT02136134
Other Study ID Numbers: CR103995
First Submitted: May 1, 2014
First Posted: May 12, 2014
Results First Posted: February 10, 2017
Last Update Posted: March 13, 2024
Last Verified: March 2024
History of Changes

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Study 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.
Condition or Disease Intervention/Treatment
  • Multiple Myeloma
  • Drug: Daratumumab
  • Drug: VELCADE (Bortezomib)
  • Drug: Dexamethasone

Study Design

Study TypeInterventional
Actual Enrollment498 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitlePhase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma
Study Start DateAugust 15, 2014
Actual Primary Completion DateJanuary 11, 2016
Actual Study Completion DateJanuary 12, 2024

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • Daratumumab+VELCADE+dexamethasone
    • Daratumumab, VELCADE and dexamethasone
  • Drug: 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.
  • Drug: VELCADE (Bortezomib)
    • Drug: Dexamethasone
      • VELCADE+dexamethasone
        • VELCADE and dexamethasone.
      • Drug: VELCADE (Bortezomib)
        • Drug: Dexamethasone

          Outcome Measures

          Primary Outcome Measures

          1. Progression-free Survival (PFS) [From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)]
            PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one 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-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved 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) that can be attributed solely to PC proliferative disorder.

          Secondary Outcome Measures

          1. Time to Disease Progression (TTP) [From the date of randomization to the date of first documented evidence of progression or death due to PD whichever occurred first (approximately 6 years 9 months)]
            TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; 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 milligram per deciliter (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) that can be attributed solely to Plasma Cell (PC) proliferative disorder.
          2. Percentage of Participants With a Very Good Partial Response (VGPR) or Better [Up to disease progression (approximately 6 years 9 months)]
            Response rate of VGPR or better was defined as the percentage of participants who achieved VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.
          3. Overall Response Rate (ORR) [Up to disease progression (approximately 6 years 9 months)]
            The Overall response rate was defined as the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
          4. Percentage of Participants With Negative Minimal Residual Disease (MRD) [Up to disease progression (approximately 6 years 9 months)]
            The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR). IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR plus normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.
          5. Overall Survival (OS) [Up to 6 years 9 months]
            Overall Survival was measured from the date of randomization to the date of the participant's death.

          Eligibility Criteria

          Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
          Sexes Eligible for Study All
          Accepts Healthy Volunteers No
          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

          Contacts and Locations

          Sponsors and Collaborators 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,
          • | Sao Paulo, Brazil,
          • | São Paulo, Brazil,
          • | Brno, Czechia,
          • | Hradec Kralove, Czechia,
          • | Ostrava-Poruba, Czechia,
          • | Praha 10, Czechia,
          • | Praha 2, Czechia,
          • | Bamberg, Germany,
          • | Berlin, Germany,
          • | Duesseldorf, Germany,
          • | Freiburg, Germany,
          • | Göttingen, Germany,
          • | Hamburg, Germany,
          • | Mainz, Germany,
          • | München, Germany,
          • | Stuttgart, Germany,
          • | Tübingen, Germany,
          • | Ulm, Germany,
          • | Würzburg, Germany,
          • | Budapest, Hungary,
          • | Debrecen, Hungary,
          • | Győr, Hungary,
          • | Pecs, Hungary,
          • | Veszprém, Hungary,
          • | Busan, Korea, Republic of,
          • | Hwasun, Korea, Republic of,
          • | Seoul, Korea, Republic of,
          • | Suwon, Korea, Republic of,
          • | Ulsan, Korea, Republic of,
          • | Huixquilucan, Mexico,
          • | Monterrey, Mexico,
          • | Alkmaar, Netherlands,
          • | Amersfoort, Netherlands,
          • | Den Haag, Netherlands,
          • | Dordrecht, Netherlands,
          • | Groningen, Netherlands,
          • | Leiden, Netherlands,
          • | Maastricht, Netherlands,
          • | Nijmegen, Netherlands,
          • | Chorzów, Poland,
          • | Katowice, Poland,
          • | Krakow, Poland,
          • | Poznan, Poland,
          • | Warszawa, Poland,
          • | Krasnodar, Russian Federation,
          • | Moscow, Russian Federation,
          • | Nizhny Novgorod, Russian Federation,
          • | Penza, Russian Federation,
          • | Pyatigorsk, Russian Federation,
          • | Ryazan, Russian Federation,
          • | Samara, Russian Federation,
          • | Sochi, Russian Federation,
          • | Syktyvkar, Russian Federation,
          • | Madrid, Spain,
          • | Salamanca, Spain,
          • | San Sebastian de los Reyes, Spain,
          • | Toledo, Spain,
          • | Valencia, Spain,
          • | Linkoping, Sweden,
          • | Lulea, Sweden,
          • | Lund, Sweden,
          • | Orebro, Sweden,
          • | Sundsvall, Sweden,
          • | Umea, Sweden,
          • | Uppsala, Sweden,
          • | Västerås, Sweden,
          • | Ankara, Turkey,
          • | Istanbul, Turkey,
          • | Izmir, Turkey,
          • | Kayseri, Turkey,
          • | Kocaeli, Turkey,
          • | Malatya, Turkey,
          • | Cherkasy, Ukraine,
          • | Dnepropetrovsk, Ukraine,
          • | Ivano-Frankivsk, Ukraine,
          • | Kiev, Ukraine,
          • | Lviv, Ukraine,
          • | Poltava, Ukraine,
          • | Vinnitsa, Ukraine,
          • | Zaporizhzhya, Ukraine,
          Investigators

            More Information

            Publications

            Additional Relevant MeSH Terms

            • Multiple Myeloma
            • Neoplasms, Plasma Cell
            • Neoplasms by Histologic Type
            • Neoplasms
            • Hemostatic Disorders
            • Vascular Diseases
            • Cardiovascular Diseases
            • Paraproteinemias
            • Blood Protein Disorders
            • Hematologic Diseases
            • Hemorrhagic Disorders
            • Lymphoproliferative Disorders
            • Immunoproliferative Disorders
            • Immune System Diseases