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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02136134
• Other study ID #: CR103995
• Secondary ID: 2014-000255-8554
• Status: Completed
• Phase: Phase 3
• Start date: August 15, 2014
• Est. completion date: January 12, 2024

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01620879

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: January 12, 2024
• Est. primary completion date: January 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	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.	From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)
Secondary	Time to Disease Progression (TTP)	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.	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)
Secondary	Percentage of Participants With a Very Good Partial Response (VGPR) or Better	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.	Up to disease progression (approximately 6 years 9 months)
Secondary	Overall Response Rate (ORR)	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.	Up to disease progression (approximately 6 years 9 months)
Secondary	Percentage of Participants With Negative Minimal Residual Disease (MRD)	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.	Up to disease progression (approximately 6 years 9 months)
Secondary	Overall Survival (OS)	Overall Survival was measured from the date of randomization to the date of the participant's death.	Up to 6 years 9 months