TriangleNCT02136134 · CITED IN SOURCE DOCUMENTS
Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-08-29
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS)
Time to Disease Progression (TTP)
Percentage of Participants With a Very Good Partial Response (VGPR) or Better
Overall Response Rate (ORR)
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Overall Survival (OS)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Daratumumab, VELCADE and dexamethasone
- intervention Names
- Drug: Daratumumab
- Drug: VELCADE (Bortezomib)
- Drug: Dexamethasone
- label
- Daratumumab+VELCADE+dexamethasone
- type
- EXPERIMENTAL
- description
- VELCADE and dexamethasone.
- intervention Names
- Drug: VELCADE (Bortezomib)
- Drug: Dexamethasone
- label
- VELCADE+dexamethasone
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Daratumumab+VELCADE+dexamethasone
- description
- 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.
- name
- Daratumumab
- type
- DRUG
- arm Group Labels
- Daratumumab+VELCADE+dexamethasone
- VELCADE+dexamethasone
- description
- 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.
- name
- VELCADE (Bortezomib)
- other Names
- VELCADE
- type
- DRUG
- arm Group Labels
- Daratumumab+VELCADE+dexamethasone
- VELCADE+dexamethasone
- description
- 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.
- name
- Dexamethasone
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 498
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Progression-free Survival (PFS)
- time Frame
- From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)
- secondary Outcomes
- description
- 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.
- measure
- Time to Disease Progression (TTP)
- time Frame
- 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)
- description
- 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.
- measure
- Percentage of Participants With a Very Good Partial Response (VGPR) or Better
- time Frame
- Up to disease progression (approximately 6 years 9 months)
- description
- 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.
- measure
- Overall Response Rate (ORR)
- time Frame
- Up to disease progression (approximately 6 years 9 months)
- description
- 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.
- measure
- Percentage of Participants With Negative Minimal Residual Disease (MRD)
- time Frame
- Up to disease progression (approximately 6 years 9 months)
- description
- Overall Survival was measured from the date of randomization to the date of the participant's death.
- measure
- Overall Survival (OS)
- time Frame
- Up to 6 years 9 months
Full study description
- 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.
Source references
- references
- citation
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- type
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Source notices and limitations
Discovery and provenance
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- .8+ months) and was 17.4 months (range: 1.4 to 18.5+ months) in the Rd group. Figure 6 Figure 7 Combination Treatment with Bortezomib and Dexamethasone CASTOR (NCT02136134), an open-label, randomized, active-controlled Phase 3 trial, compared treatment with DARZALEX 16 mg/kg in combination with bortezomib and dexamethasone (DVd),
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- Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Health Professional Version
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- Updated: April 25, 2025
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- 2025-04-25T12:00:00Z
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- April 25, 2025
Preserved source evidence · Not medical advice