Phase 3
Completed N=706
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
Source: ClinicalTrials.gov NCT02195479 ↗Enrolled (actual)
706
Serious AEs
43.3%
Results posted
Dec 2018
Primary outcomePrimary: Progression Free Survival (PFS) — 18.14; NA Months
◆ Published Evidence
Highly cited
141citations · ~35 / year
Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE.
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).
Linked Publications (5)
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Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE.
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Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA.
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Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE.
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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.
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Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) |
18.14; NA | — |
| SECONDARY Overall Response Rate (ORR) |
73.9; 90.9 | — |
| SECONDARY Percentage of Participants With Very Good Partial Response (VGPR) or Better |
49.7; 71.1 | — |
| SECONDARY Percentage of Participants With Complete Response (CR) or Better |
24.4; 42.6 | — |
| SECONDARY Percentage of Participants With Stringent Complete Response (sCR) |
7.0; 18.0 | — |
| SECONDARY Percentage of Participants With Negative Minimal Residual Disease (MRD) |
7.0; 28.3 | — |
| SECONDARY Overall Survival (OS) |
53.59; 82.96 | — |
| SECONDARY Progression Free Survival on Next Line of Therapy (PFS2) |
42.41; 66.73 | — |
| SECONDARY Time to Disease Progression (TTP) |
19.35; NA | — |
| SECONDARY Time to Response |
0.82; 0.79 | — |
| SECONDARY Duration of Response (DOR) |
21.3; NA | — |
| SECONDARY Time to Next Treatment (TNT) |
25.9; 66.8 | — |
| SECONDARY Percentage of Participants With Best M-protein Response |
38.7; 58.5; 14.6; 15.2; 69.4; 90.5 | — |
| SECONDARY Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score |
9.4; 8.5; 10.5; 10.8; 11.8; 11.1 | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Global Health Scale |
4; 7.5; 8.8; 8.5; 10.2; 10.6 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS) |
4.27; 9.37; 7.51; 11.02; 10.08; 12.51 | — |
| SECONDARY Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score |
0.09; 0.12; 0.12; 0.14; 0.16; 0.16 | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT02195479) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.