Clinical trial NCT02136134: Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
Official title: Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Plasmacytoma
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Daratumumab
VELCADE
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-05-12
Enrollment: 498
Sex: ALL
Minimum age (years): 18
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 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.

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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)
Secondary outcomes:
measure: Time to Disease Progression (TTP)
timeFrame: 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)
measure: Percentage of Participants With a Very Good Partial Response (VGPR) or Better
timeFrame: Up to disease progression (approximately 6 years 9 months)
measure: Overall Response Rate (ORR)
timeFrame: Up to disease progression (approximately 6 years 9 months)
measure: Percentage of Participants With Negative Minimal Residual Disease (MRD)
timeFrame: Up to disease progression (approximately 6 years 9 months)
measure: Overall Survival (OS)
timeFrame: Up to 6 years 9 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Stamford
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Niles
country: United States
state: Illinois
city: Topeka
country: United States
state: Kansas
city: Westwood
country: United States
state: Kansas
city: Marrero
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Seattle
country: United States
state: Washington
city: Adelaide
country: Australia
city: Concord
country: Australia
city: Fitzroy
country: Australia
city: Hobart
country: Australia
city: Melbourne
country: Australia
city: Nedlands
country: Australia
city: Woodville South
country: Australia
city: Barretos
country: Brazil
city: Porto Alegre
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Ostrava-Poruba
country: Czechia
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Bamberg
country: Germany
city: Berlin
country: Germany
city: Duesseldorf
country: Germany
city: Freiburg
country: Germany
city: Göttingen
country: Germany
city: Hamburg
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Stuttgart
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Würzburg
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Győr
country: Hungary
city: Pecs
country: Hungary
city: Veszprém
country: Hungary
city: Busan
country: Korea, Republic of
city: Hwasun
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Ulsan
country: Korea, Republic of
city: Huixquilucan
country: Mexico
city: Monterrey
country: Mexico
city: Alkmaar
country: Netherlands
city: Amersfoort
country: Netherlands
city: Den Haag
country: Netherlands
city: Dordrecht
country: Netherlands
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Chorzow
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Krasnodar
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Penza
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Samara
country: Russian Federation
city: Sochi
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: San Sebastian de los Reyes
country: Spain
city: Toledo
country: Spain
city: Valencia
country: Spain
city: Linkoping
country: Sweden
city: Lulea
country: Sweden
city: Lund
country: Sweden
city: Orebro
country: Sweden
city: Sundsvall
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Västerås
country: Sweden
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
city: Kocaeli
country: Turkey
city: Malatya
country: Turkey
city: Cherkasy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Poltava
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zaporizhzhya
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical trial
role: STUDY_DIRECTOR
References:
citation: He J, Berringer H, Heeg B, Ruan H, Kampfenkel T, Dwarakanathan HR, Johnston S, Mendes J, Lam A, Bathija S, Mackay EK. Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma. Adv Ther. 2022 Sep;39(9):4230-4249. doi: 10.1007/s12325-022-02226-x. Epub 2022 Jul 22.
citation: Cavo M, San-Miguel J, Usmani SZ, Weisel K, Dimopoulos MA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria V, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar S, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi N. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2022 Feb 10;139(6):835-844. doi: 10.1182/blood.2021011101.
citation: Avet-Loiseau H, San-Miguel J, Casneuf T, Iida S, Lonial S, Usmani SZ, Spencer A, Moreau P, Plesner T, Weisel K, Ukropec J, Chiu C, Trivedi S, Amin H, Krevvata M, Ramaswami P, Qin X, Qi M, Sun S, Qi M, Kobos R, Bahlis NJ. Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR. J Clin Oncol. 2021 Apr 1;39(10):1139-1149. doi: 10.1200/JCO.20.01814. Epub 2021 Jan 29.
citation: Weisel K, Spencer A, Lentzsch S, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka A, Quach H, Munder M, Lee C, Barreto W, Corradini P, Min CK, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Jo JC, Shin HJ, Sonneveld P, Casneuf T, DeAngelis N, Amin H, Ukropec J, Kobos R, Mateos MV. Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. J Hematol Oncol. 2020 Aug 20;13(1):115. doi: 10.1186/s13045-020-00948-5.
citation: Mateos MV, Spencer A, Nooka AK, Pour L, Weisel K, Cavo M, Laubach JP, Cook G, Iida S, Benboubker L, Usmani SZ, Yoon SS, Bahlis NJ, Chiu C, Ukropec J, Schecter JM, Qin X, O'Rourke L, Dimopoulos MA. Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica. 2020 Jan 31;105(2):468-477. doi: 10.3324/haematol.2019.217448. Print 2020.
citation: Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. doi: 10.1056/NEJMoa1606038.