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

• Register: EUCTR
• Last refreshed on: 17 August 2021
• Main ID: EUCTR2014-000255-85-HU
• Date of registration: 12/08/2014
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants with Relapsed or Refractory Multiple Myeloma
• Scientific title: Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma
• Date of first enrolment: 30/09/2014
• Target sample size: 480
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000255-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 192
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 288

Exclusion criteria:
-Has received daratumumab or other anti­CD38 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 anti­myeloma treatment within 2 weeks or 5 pharmacokinetic half­lives 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 anti­myeloma treatments with the corresponding pharmacokinetic half­lives 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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple myeloma
MedDRA version: 19.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Daratumumab
Product Code: HuMax-CD38
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Current Sponsor code: JNJ-54767414 (Daratumumab)
Other descriptive name: HUMAX-CD38
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): Percentage of participants with progression-free survival (PFS)

Main Objective: To compare the efficacy of daratumumab when combined with VELCADE and dexamethasone (DVd) to that of VELCADE and dexamethasone (Vd), in terms of progression-free survival (PFS) in subjects with relapsed or refractory multiple myeloma.

Secondary Objective: The major secondary objectives are as follows:
- To evaluate clinical outcomes including time to disease progression (TTP), overall response rate (ORR), and overall survival (OS).
- To evaluate the proportion of subjects with a response of very good partial response (VGPR) or better.
- To evaluate duration of and time to response.
- To assess the safety and tolerability of daratumumab when administered in combination with Vd.
- To assess Minimal Residual Disease (MRD) in subjects who achieve =VGPR.
- To assess the pharmacokinetics of daratumumab in combination with Vd.
- To assess the immunogenicity of daratumumab.
- To evaluate treatment effects on patient reported outcomes (PROs) including the EuroQol-5 Dimensions (EQ-5D-5L) and EORTC QLQ-C30.
- To evaluate clinical efficacy of DVd in high risk molecular subgroups (del17p, t(4;14), t(14;20), UAMS-70).

Timepoint(s) of evaluation of this end point: Baseline, up to the end of the study

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - For all secondary end points except 4 is Baseline, up to the end of the study
- for secondary end point 4 is Baseline until first documented response

Secondary end point(s): 1. Time to disease progression (TTP)
2. Percentage of Participants With Overall Response
3. Duration of response
4. Time to Response
5. Percentage of participants with a very good partial response (VGPR) or better
6. Percentage of participants with Minimal Residual Disease (MRD)
7. Percentage of participants with overall survival (OS)

Secondary ID(s)

54767414MMY3004

2014-000255-85-DE

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 12/09/2014
Contact: