A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma
A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy
3 other identifiers
interventional
706
24 countries
160
Brief Summary
The purpose of this study is to determine if the addition of daratumumab to velcade (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared with VMP alone in participants with previously untreated multiple myeloma who are ineligible for high dose chemotherapy and autologous stem cell transplant (ASCT).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started Dec 2014
Longer than P75 for phase_3 multiple-myeloma
160 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 18, 2014
CompletedFirst Posted
Study publicly available on registry
July 21, 2014
CompletedStudy Start
First participant enrolled
December 9, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 21, 2017
CompletedResults Posted
Study results publicly available
December 17, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 7, 2024
CompletedAugust 22, 2025
August 1, 2025
3 years
July 18, 2014
November 21, 2018
August 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS: duration from date of randomization to progressive disease (PD)/death, whichever occurs first. PD per IMWG criteria-Increase of 25% from lowest response value in one of following: Serum M-component (absolute increase \>=0.5 grams per deciliter \[g/dL\]); Urine M-component (absolute increase \>=200 milligrams \[mg\]/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase \>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow Plasma cells (PC) percentage (%) (absolute % \>=10%); Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.
From randomization (Day -3) up to 2.4 years
Secondary Outcomes (16)
Overall Response Rate (ORR)
From randomization (Day -3) up to 2.4 years
Percentage of Participants With Very Good Partial Response (VGPR) or Better
From randomization (Day -3) up to 2.4 years
Percentage of Participants With Complete Response (CR) or Better
From randomization (Day -3) up to 2.4 years
Percentage of Participants With Stringent Complete Response (sCR)
From randomization (Day -3) up to 2.4 years
Percentage of Participants With Negative Minimal Residual Disease (MRD)
From randomization (Day -3) up to 8.3 years
- +11 more secondary outcomes
Study Arms (2)
Treatment Arm A (VMP Alone)
ACTIVE COMPARATORParticipants will receive velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 , orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.
Treatment Arm B (D-VMP)
EXPERIMENTALParticipants will receive velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. In addition participants will also receive daratumumab 16 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. On days when daratumumab is given, dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute, and prednisone 60 mg/m2 once daily will be given on Days 2-4. Following amendment 7, participants will have the option to switch to daratumumab subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
Interventions
Participants will receive velcade 1.3 mg/m\^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.
Participants will receive melphalan 9 mg/m\^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.
Participants will receive prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.
Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study .
Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute.
Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC.
Eligibility Criteria
You may qualify if:
- Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol
- Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age \>=65 years, or in participants \<65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Meet the clinical laboratory criteria as specified in the protocol
- A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
- Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy
You may not qualify if:
- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
- Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
- Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
- Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
- Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
- Participant has had radiation therapy within 14 days of randomization
- Participant has had plasmapheresis within 28 days of randomization
- Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed)
- Participants with known or suspected COPD must have a FEV1 test during screening
- Participant is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or history of to have a history of hepatitis C
- Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (160)
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California City, California, United States
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Corona, California, United States
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Fountain Valley, California, United States
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Los Angeles, California, United States
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Hialeah, Florida, United States
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Springfield, Missouri, United States
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Cleveland, Ohio, United States
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Buenos Aires, Argentina
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Ciudad Autonoma Buenos Aires, Argentina
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Córdoba, Argentina
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Santa Fe, Argentina
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Adelaide, Australia
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Bendigo, Australia
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Camperdown, Australia
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Geelong, Australia
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Greenslopes, Australia
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Hobart, Australia
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North Adelaide, Australia
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Parkville, Australia
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Antwerp, Belgium
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Brussels, Belgium
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Charleroi, Belgium
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Ghent, Belgium
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Kortrijk, Belgium
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Roeselare, Belgium
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Turnhout, Belgium
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Yvoir, Belgium
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Barretos, Brazil
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Cuiaba - Mount, Brazil
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Fortaleza, Brazil
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Goiânia, Brazil
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Natal, Brazil
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Porto Alegre, Brazil
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Ribeirão Preto, Brazil
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Rio de Janeiro, Brazil
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São Paulo, Brazil
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Pleven, Bulgaria
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Plovdiv, Bulgaria
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Sofia, Bulgaria
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Varna, Bulgaria
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Vratsa, Bulgaria
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Zadar, Croatia
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Zagreb, Croatia
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Brno, Czechia
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Hradec Králové, Czechia
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Olomouc, Czechia
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Ostrava-Poruba, Czechia
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Prague, Czechia
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Tbilisi, Georgia
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Berlin, Germany
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Dortmund, Germany
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Karlsruhe, Germany
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Potsdam, Germany
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Saarbrücken, Germany
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Würzburg, Germany
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Athens, Greece
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Athens Attica, Greece
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Pátrai, Greece
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Thessaloniki, Greece
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Budapest, Hungary
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Debrecen, Hungary
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Kaposvár, Hungary
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Pécs, Hungary
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Chiba, Japan
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Hitachi, Japan
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Kanazawa, Japan
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Kawasaki, Japan
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Kobe, Japan
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Kurume, Japan
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Matsuyama, Japan
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Nagoya, Japan
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Narita, Japan
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Ohgaki, Japan
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Okayama, Japan
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Osaka, Japan
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Sendai, Japan
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Shibukawa, Japan
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Shibuya City, Japan
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Tachikawa, Japan
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Toyohashi, Japan
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Skopje, North Macedonia
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Bialystok, Poland
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Bydgoszcz, Poland
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Chorzów, Poland
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Gdansk, Poland
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Legnica, Poland
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Lublin, Poland
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Opole, Poland
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Słupsk, Poland
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Warsaw, Poland
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Warszawa Ul, Poland
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Wroclaw, Poland
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Lisbon, Portugal
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Porto, Portugal
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Brasov, Romania
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Bucharest, Romania
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Iași, Romania
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Arkhangelsk, Russia
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Dzerzhinsk, Russia
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Nizhny Novgorod, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Sochi, Russia
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Volgograd, Russia
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Yekaterinburg, Russia
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Belgrade, Serbia
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Kamenitz, Serbia
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Niš, Serbia
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Novi Sad, Serbia
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Zemun, Serbia
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Busan, South Korea
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Gyeonggi-do, South Korea
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Hwasun, South Korea
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Incheon, South Korea
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Seongnam, South Korea
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Seoul, South Korea
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Andalucía, Spain
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Badalona, Spain
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Barcelona, Spain
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Córdoba, Spain
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Girona, Spain
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Madrid, Spain
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Marañón, Spain
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Murcia, Spain
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Ourense, Spain
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Pamplona, Spain
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Salamanca, Spain
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San Cristóbal de La Laguna, Spain
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Seville, Spain
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Toledo, Spain
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Zaragoza, Spain
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Altındağ, Turkey (Türkiye)
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Aydin, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Samsun, Turkey (Türkiye)
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Tekirdağ, Turkey (Türkiye)
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Cherkassy, Ukraine
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Lviv, Ukraine
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Zaporizhzhia, Ukraine
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Birmingham, United Kingdom
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Harlow, United Kingdom
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Leicester, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Woolwich, United Kingdom
Related Publications (7)
Mateos MV, San-Miguel J, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Yoon SS, Iosava G, Fujisaki T, Garg M, Ngo M, Katz EG, Krevvata M, Bolyard K, Carson R, Borgsten F, Dimopoulos MA. Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible patients with newly diagnosed multiple myeloma (ALCYONE): final analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2025 May;26(5):596-608. doi: 10.1016/S1470-2045(25)00018-X. Epub 2025 Apr 9.
PMID: 40220771DERIVEDMateos MV, Dimopoulos MA, Cavo M, Suzuki K, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Yoon SS, Iosava G, Fujisaki T, Garg M, Iida S, Blade J, Ukropec J, Pei H, Van Rampelbergh R, Kudva A, Qi M, San-Miguel J. Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):785-798. doi: 10.1016/j.clml.2021.06.005. Epub 2021 Jun 18.
PMID: 34344638DERIVEDCavo 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.
PMID: 34289038DERIVEDSan-Miguel J, Avet-Loiseau H, Paiva B, Kumar S, Dimopoulos MA, Facon T, Mateos MV, Touzeau C, Jakubowiak A, Usmani SZ, Cook G, Cavo M, Quach H, Ukropec J, Ramaswami P, Pei H, Qi M, Sun S, Wang J, Krevvata M, DeAngelis N, Heuck C, Van Rampelbergh R, Kudva A, Kobos R, Qi M, Bahlis NJ. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022 Jan 27;139(4):492-501. doi: 10.1182/blood.2020010439.
PMID: 34269818DERIVEDKnop S, Mateos MV, Dimopoulos MA, Suzuki K, Jakubowiak A, Doyen C, Lucio P, Nagy Z, Usenko G, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Losava G, Fujisaki T, Garg M, Wang J, Wroblewski S, Kudva A, Gries KS, Fastenau J, San-Miguel J, Cavo M. Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial. BMC Cancer. 2021 Jun 2;21(1):659. doi: 10.1186/s12885-021-08325-2.
PMID: 34078314DERIVEDMateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Krevvata M, Chen Y, Wang J, Kudva A, Ukropec J, Wroblewski S, Qi M, Kobos R, San-Miguel J. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020 Jan 11;395(10218):132-141. doi: 10.1016/S0140-6736(19)32956-3. Epub 2019 Dec 10.
PMID: 31836199DERIVEDMateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. doi: 10.1056/NEJMoa1714678. Epub 2017 Dec 12.
PMID: 29231133DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Executive Medical Director
- Organization
- Janssen Research and Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 18, 2014
First Posted
July 21, 2014
Study Start
December 9, 2014
Primary Completion
November 21, 2017
Study Completion
August 7, 2024
Last Updated
August 22, 2025
Results First Posted
December 17, 2018
Record last verified: 2025-08