A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
The purpose of this study is to compare the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma.
Inclusion Criteria
- Must have documented multiple myeloma and measurable disease
- Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
- Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
- Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a "wash-out period" defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy
Exclusion Criteria
- Has received any of the following therapies: daratumumab or other anti-CD38 therapies
- Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment
- Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
- Has received autologous stem cell transplantation within 12 weeks before the date of randomization, or previously received an allogenic stem cell transplant (regardless of timing), or planning to undergo a stem cell transplant prior to progression of disease
- History of malignancy (other than multiple myeloma) within 5 years before the first dose of daratumumab monotherapy (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
Additional locations may be listed on ClinicalTrials.gov for NCT02076009.
See trial information on ClinicalTrials.gov for a list of participating sites.
This is a randomized (participants will be assigned by chance to study treatments),
open-label (all participants and study personnel will know the identity of the study
treatments), active-controlled (none of the study treatments are placebo), parallel-group
(both treatment arms will run at the same time), multicenter study. In this study,
daratumumab, lenalidomide, and low-dose dexamethasone (DRd) will be compared with
lenalidomide and low dose dexamethasone (Rd) in participants with relapsed or refractory
multiple myeloma. Participants will be randomized in a 1:1 ratio to receive either DRd or
Rd. The study will include a Screening Phase, a Treatment Phase (involving treatment
cycles of approximately 28 days in length), and a Follow-up Phase. The Treatment Phase
will extend from the administration of the first dose of study medication until disease
progression or unacceptable toxicity. Participants will also discontinue study treatment
if: they become pregnant; have their dose held for more than 28 days (or if 3 consecutive
planned doses of daratumumab are missed for reasons other than toxicity); or for safety
reasons (for example, adverse event). The Follow-up Phase will begin at the end of
treatment and will continue until death, loss to follow-up, consent withdrawal for study
participation, or the final overall survival (OS) analysis, whichever occurs first.
Eligible participants from Rd group who have had sponsor confirmed disease progression
will be offered the option for treatment with daratumumab monotherapy (of 28 days cycle).
The primary endpoint will be progression-free survival (PFS). Analysis of the primary
endpoint was performed at a pre-specified point determined by PFS events with a clinical
cutoff of March 7, 2016 when 169 events of death or progression had occurred. The end of
study is anticipated at approximately 6 years after the last participant is randomized.
Blood and urine samples will be obtained at time points during the study, together with
bone marrow aspirates/biopsies and skeletal surveys. Participant safety will be assessed
throughout the study.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationJanssen Pharmaceuticals
- Primary IDCR103663
- Secondary IDsNCI-2014-01352, 2013-005525-23, 54767414MMY3003, s14-01195
- ClinicalTrials.gov IDNCT02076009