Clinical trial NCT02874742: Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma
Official title: Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy and Autologous Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-08-22
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.


Eligibility criteria: Inclusion Criteria:

* Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
* Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram \[mg\] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin \[b-hCG\]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
* A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose

Exclusion Criteria:

* Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (\>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
* Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
* Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (\<)50 percent (%) of predicted normal
* Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
* Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study

Primary outcomes:
measure: Percentage of Participants With Stringent Complete Response (sCR)
timeFrame: From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)
Secondary outcomes:
measure: Percentage of Participants With Complete Response (CR) or Better
timeFrame: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)
measure: Percentage of Participants With Overall Stringent Complete Response (sCR)
timeFrame: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)
measure: Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
timeFrame: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)
measure: Percentage of Participants With Negative Minimal Residual Disease (MRD)
timeFrame: From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months), and at the end of maintenance period of 24 months (overall duration up to 34 months)
measure: Duration of Complete Response or Better
timeFrame: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)
measure: Duration of Stringent Complete Response (sCR)
timeFrame: From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)
measure: Time to Stringent Complete Response (sCR)
timeFrame: From randomization to the date of initial documentation of sCR (up to 5 years)
measure: Time to Complete Response or Better
timeFrame: From randomization to the date of initial documentation of CR (up to 5 years)
measure: Time to Very Good Partial Response (VGPR) or Better
timeFrame: From randomization to the date of initial documentation of VGPR or better (up to 5 years)
measure: Time to Partial Response (PR) or Better
timeFrame: From randomization to the date of initial documentation of PR or better (up to 5 years)
measure: Progression-free Survival (PFS)
timeFrame: From randomization to the date of first documented evidence of progressive disease or death (up to 5 years)
measure: Overall Survival (OS)
timeFrame: From randomization to the date of initial documentation of participant's death (up to 5 years)
measure: Time to Progression (TTP)
timeFrame: From randomization to the date of first documented evidence of progressive disease (up to 5 years)
measure: Duration of Response
timeFrame: From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 5 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Duarte
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Westwood
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Abington
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sborov DW, Baljevic M, Reeves B, Laubach J, Efebera YA, Rodriguez C, Costa LJ, Chari A, Silbermann R, Holstein SA, Anderson LD Jr, Kaufman JL, Shah N, Pei H, Patel S, Cortoos A, Bartlett JB, Vermeulen J, Lin TS, Voorhees PM, Richardson PG. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022 Nov;199(3):355-365. doi: 10.1111/bjh.18432. Epub 2022 Sep 16.
citation: Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.
citation: Voorhees PM, Rodriguez C, Reeves B, Nathwani N, Costa LJ, Lutska Y, Bobba P, Hoehn D, Pei H, Ukropec J, Qi M, Lin TS, Richardson PG. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.
citation: Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Murphy S, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin TS, Richardson PG. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945. doi: 10.1182/blood.2020005288.