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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02195479
Collaborator
(none)
706
Enrollment
165
Locations
2
Arms
102.7
Anticipated Duration (Months)
4.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone and Treatment B: participants will receive daratumumab in combination with VMP).Two interim analyses are planned. The first will be to evaluate safety after a total of approximately 100 participants have been treated for at least 2 cycles or discontinued the study treatment. The second will be to evaluate cumulative interim safety and efficacy data, and will be performed when approximately 216 PFS events have been accumulated. The final OS analysis will occur when approximately 382 deaths have occurred. Efficacy will be primarily measured by comparison of PFS between the two treatment arms. Participants' safety will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
706 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Dec 9, 2014
Actual Primary Completion Date :
Nov 21, 2017
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Treatment Arm A (VMP Alone)

Participants 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.

Drug: Velcade
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.

Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Experimental: Treatment Arm B (D-VMP)

Participants 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.

Drug: Velcade
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.

Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Daratumumab IV
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 .

Drug: Dexamethasone
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.

Drug: Daratumumab SC
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.

Outcome Measures

Primary Outcome Measures

  1. Progression Free Survival (PFS) [From randomization to either disease progression or death whichever occurs first (up to 2.4 years)]

    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 and urine M-component (absolute increase >=0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); 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) %(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.

Secondary Outcome Measures

  1. Overall Response Rate (ORR) [From randomization to disease progression (up to 2.4 years)]

    The Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better, according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: greater than or equal to (>=) 50 percentage(%) reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

  2. Percentage of Participants With Very Good Partial Response (VGPR) or Better [From randomization to disease progression (up to 2.4 years)]

    VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response[sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram (mg) per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and < 5% plasms cells (PCs) in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

  3. Percentage of Participants With Complete Response (CR) or Better [From randomization to disease progression (up to 2.4 years)]

    CR or better rate was defined as the percentage of participants with a CR or better (i.e. CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

  4. Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to disease progression (up to 2.4 years)]

    The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^-5 threshold. MRD was evaluated by using Deoxyribonucleic acid (DNA) sequencing of immunoglobulin genes. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR).

  5. Overall Survival (OS) [From randomization to death (up to approximately 2.4 years)]

    Overall Survival (OS) was defined as the number of days the date of randomization to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.

  6. Progression Free Survival on Next Line of Therapy (PFS2) [From randomization to either disease progression or death whichever occurs first (up to 2.4 years)]

    Progression-free survival after next-line therapy is defined as the time from randomization to progression on the next line of subsequent antimyeloma therapy or death due to any cause (prior to start of second line of antimyeloma therapy), whichever comes first. Disease progression on next line of treatment was based on investigator judgment.

  7. Percentage of Participants With Stringent Complete Response (sCR) [From randomization to disease progression (up to 2.4 years)]

    sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. CR: Negative immunofixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; <5% plasma cells (PCs) in bone marrow.

  8. Time to Disease Progression (TTP) [From randomization to either disease progression or death due to PD whichever occurs first (up to 2.4 years)]

    TTP: Time from date of randomization to date of first documented evidence of PD or death due to PD, whichever occurs first. PD per IMWG criteria- Increase of 25 % from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase >10 milligram per deciliter [mg/dL]); Only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cells (PC)% (absolute % >=10%); Bone marrow PC %: absolute % >10%; Definite development of new bone lesions/soft tissue plasmacytomas or 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.

  9. Time to Response [From randomization to first documented PR or better (up to 2.4 years)]

    Time to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%.

  10. Duration of Response (DOR) [Up to 2.4 years]

    DOR: participants with a confirmed response (PR or better) as time between first documentation of response and disease progression, IMWG response criteria, or death due to PD, whichever occurs first. PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase>=0.5 g/dL); Urine M-component (absolute increase>=200 mg/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); Only participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC%(absolute%>=10%); Bone marrow PC's %: absolute%>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in the size of existing bone lesions or soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  11. Time to Next Treatment (TNT) [Approximately up to 2.4 years]

    Time to next treatment is defined as the time from randomization to the start of the next-line treatment.

  12. Percentage of Participants With Best M-protein Response [Approximately up to 2.4 years]

    Percentage of participants with Best M- protein response of 100% reduction and >=90% to < 100% reduction were assessed. Best M-protein response was defined as the maximal percent reduction or the lowest percent increase from baseline in serum M-protein for participants with measurable heavy chain at baseline or urine M-protein for participants without measurable heavy chain, but with measurable light chain disease at baseline. For participants without measurable heavy chain and light chain disease at baseline, best response in serum free light chain (FLC) was defined as the maximal percent reduction or the lowest percent increase from baseline in the difference between involved and uninvolved serum FLC level (dFLC).

  13. Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score [Baseline, Months 3, 6, 9, 12 and 18]

    The EORTC QLQ-C30 is a 30 items self-reporting questionnaire, with a 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores are transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values indicate deterioration in quality of life or functioning and positive values indicate improvement.

  14. Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS) [Baseline, Months 3, 6, 9, 12 and 18]

    EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

  15. Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score [Baseline, Months 3, 6, 9, 12 and 18]

    EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 this study

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1California CityCaliforniaUnited States
2CoronaCaliforniaUnited States
3Fountain ValleyCaliforniaUnited States
4Los AngelesCaliforniaUnited States
5HialeahFloridaUnited States
6Orange ParkFloridaUnited States
7ChicagoIllinoisUnited States
8SpringfieldMissouriUnited States
9ClevelandOhioUnited States
10FredericksburgVirginiaUnited States
11Buenos AiresArgentina
12Ciudad Autonoma Buenos AiresArgentina
13CórdobaArgentina
14Santa FeArgentina
15AdelaideAustralia
16BendigoAustralia
17Camperdown N/aAustralia
18GeelongAustralia
19GosfordAustralia
20GreenslopesAustralia
21HobartAustralia
22North AdelaideAustralia
23ParkvilleAustralia
24AntwerpenBelgium
25AntwerpBelgium
26BrusselBelgium
27CharleroiBelgium
28GentBelgium
29KortrijkBelgium
30RoeselareBelgium
31TurnhoutBelgium
32YvoirBelgium
33BarretosBrazil
34Cuiaba - MountBrazil
35Fortaleza CearaBrazil
36FortalezaBrazil
37GoiâniaBrazil
38NatalBrazil
39Niteroi N/aBrazil
40Porto AlegreBrazil
41Riberao PretoBrazil
42Sao PauloBrazil
43PlevenBulgaria
44PlovdivBulgaria
45SofiaBulgaria
46VarnaBulgaria
47VratsaBulgaria
48ZadarCroatia
49ZagrebCroatia
50BrnoCzechia
51Hradec KraloveCzechia
52OlomoucCzechia
53Ostrava-PorubaCzechia
54Praha 10Czechia
55Praha 2Czechia
56TbilisiGeorgia
57BerlinGermany
58DortmundGermany
59KarlsruheGermany
60PotsdamGermany
61SaarbrückenGermany
62StuttgartGermany
63WürzburgGermany
64Athens AtticaGreece
65AthensGreece
66PatraGreece
67ThessalonikiGreece
68BudapestHungary
69DebrecenHungary
70KaposvarHungary
71Pecs N/aHungary
72ChibaJapan
73HitachiJapan
74KanazawaJapan
75KawasakiJapan
76KobeJapan
77KurumeJapan
78MatsuyamaJapan
79NagoyaJapan
80NaritaJapan
81OhgakiJapan
82OkayamaJapan
83OsakaJapan
84Sendai-shiJapan
85ShibukawaJapan
86ShibuyaJapan
87TachikawaJapan
88ToyohashiJapan
89BusanKorea, Republic of
90Gyeonggi-doKorea, Republic of
91HwasunKorea, Republic of
92IncheonKorea, Republic of
93SeongnamKorea, Republic of
94SeoulKorea, Republic of
95SkopjeNorth Macedonia
96BialystokPoland
97BydgoszczPoland
98ChorzowPoland
99GdanskPoland
100LegnicaPoland
101LublinPoland
102OpolePoland
103SlupskPoland
104Warszawa UlPoland
105WarszawaPoland
106WroclawPoland
107LisboaPortugal
108LisbonPortugal
109PortoPortugal
110BrasovRomania
111BucharestRomania
112IasiRomania
113ArkhangelskRussian Federation
114DzerzhinskRussian Federation
115EkaterinbourgRussian Federation
116Nizhny NovgorodRussian Federation
117RyazanRussian Federation
118Saint-PetersburgRussian Federation
119SaratovRussian Federation
120SochiRussian Federation
121St PetersburgRussian Federation
122VolgogradRussian Federation
123BelgradeSerbia
124NisSerbia
125Novi SadSerbia
126Sremska KamenicaSerbia
127ZemunSerbia
128AndalucíaSpain
129BadalonaSpain
130BarcelonaSpain
131CórdobaSpain
132GironaSpain
133La LagunaSpain
134MadridSpain
135MaranonSpain
136Murcia N/aSpain
137OurenseSpain
138PamplonaSpain
139SalamancaSpain
140SevillaSpain
141ToledoSpain
142ValenciaSpain
143ZaragozaSpain
144AltindagTurkey
145AnkaraTurkey
146AydinTurkey
147IzmirTurkey
148KayseriTurkey
149SamsunTurkey
150TekirdagTurkey
151CherkassyUkraine
152DnepropetrovskUkraine
153Ivano-FrankivskUkraine
154KharkovUkraine
155KhmelnitskiyUkraine
156LvivUkraine
157ZaporizhzhiaUkraine
158BirminghamUnited Kingdom
159CambridgeUnited Kingdom
160ColchesterUnited Kingdom
161HarlowUnited Kingdom
162LeicesterUnited Kingdom
163LondonUnited Kingdom
164ManchesterUnited Kingdom
165WoolwichUnited Kingdom

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02195479
Other Study ID Numbers:
  • CR104761
  • 54767414MMY3007
  • 2014-002272-88
First Posted:
Jul 21, 2014
Last Update Posted:
Dec 3, 2021
Last Verified:
Dec 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailResults are reported up to second interim analysis (up to 2.4 years). Complete data through 6.4 years will be reported within 1 year of end of study trial date when final data based on study completion date will be available.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Period Title: Overall Study
STARTED356350
Treated354346
COMPLETED00
NOT COMPLETED356350

Baseline Characteristics

Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)Total
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.Total of all reporting groups
Overall Participants356350706
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
71.5
(5.82)
71.3
(6.66)
71.4
(6.25)
Sex: Female, Male (Count of Participants)
Female
189
53.1%
190
54.3%
379
53.7%
Male
167
46.9%
160
45.7%
327
46.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
16
4.5%
24
6.9%
40
5.7%
Not Hispanic or Latino
332
93.3%
320
91.4%
652
92.4%
Unknown or Not Reported
8
2.2%
6
1.7%
14
2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
45
12.6%
47
13.4%
92
13%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
3
0.8%
3
0.9%
6
0.8%
White
304
85.4%
297
84.9%
601
85.1%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
4
1.1%
3
0.9%
7
1%
Region of Enrollment (Count of Participants)
Argentina
2
0.6%
2
0.6%
4
0.6%
Australia
10
2.8%
5
1.4%
15
2.1%
Belgium
8
2.2%
6
1.7%
14
2%
Brazil
2
0.6%
4
1.1%
6
0.8%
Bulgaria
15
4.2%
8
2.3%
23
3.3%
Croatia
2
0.6%
2
0.6%
4
0.6%
Czech Republic
29
8.1%
21
6%
50
7.1%
Georgia
11
3.1%
11
3.1%
22
3.1%
Germany
2
0.6%
5
1.4%
7
1%
Greece
15
4.2%
14
4%
29
4.1%
Hungary
12
3.4%
14
4%
26
3.7%
Italy
26
7.3%
28
8%
54
7.6%
Japan
26
7.3%
24
6.9%
50
7.1%
Poland
27
7.6%
39
11.1%
66
9.3%
Portugal
4
1.1%
3
0.9%
7
1%
Macedonia
10
2.8%
1
0.3%
11
1.6%
Romania
18
5.1%
10
2.9%
28
4%
Russia
21
5.9%
22
6.3%
43
6.1%
Serbia
3
0.8%
7
2%
10
1.4%
Korea, Democratic People'S Republic Of
18
5.1%
23
6.6%
41
5.8%
Spain
47
13.2%
56
16%
103
14.6%
Turkey
10
2.8%
5
1.4%
15
2.1%
Ukraine
20
5.6%
28
8%
48
6.8%
United Kingdom
15
4.2%
9
2.6%
24
3.4%
United States
3
0.8%
3
0.9%
6
0.8%
Stage of Disease (ISS) (Count of Participants)
I
38
10.7%
47
13.4%
85
12%
II
247
69.4%
226
64.6%
473
67%
III
46
12.9%
60
17.1%
106
15%
Time from multiple myeloma (MM) diagnosis (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]
1.27
(1.737)
1.09
(1.056)
1.18
(1.442)

Outcome Measures

1. Primary Outcome
TitleProgression Free Survival (PFS)
DescriptionPFS- 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 and urine M-component (absolute increase >=0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); 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) %(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.
Time FrameFrom randomization to either disease progression or death whichever occurs first (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
Intent-to-treat (ITT) population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Median (95% Confidence Interval) [Months]
18.14
NA
2. Secondary Outcome
TitleOverall Response Rate (ORR)
DescriptionThe Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better, according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: greater than or equal to (>=) 50 percentage(%) reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Time FrameFrom randomization to disease progression (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Number [Percentage of participants]
73.9
20.8%
90.9
26%
3. Secondary Outcome
TitlePercentage of Participants With Very Good Partial Response (VGPR) or Better
DescriptionVGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response[sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram (mg) per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and < 5% plasms cells (PCs) in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
Time FrameFrom randomization to disease progression (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Number [Percentage of participants]
49.7
14%
71.1
20.3%
4. Secondary Outcome
TitlePercentage of Participants With Complete Response (CR) or Better
DescriptionCR or better rate was defined as the percentage of participants with a CR or better (i.e. CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
Time FrameFrom randomization to disease progression (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Number [Percentage of participants]
24.4
6.9%
42.6
12.2%
5. Secondary Outcome
TitlePercentage of Participants With Negative Minimal Residual Disease (MRD)
DescriptionThe Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^-5 threshold. MRD was evaluated by using Deoxyribonucleic acid (DNA) sequencing of immunoglobulin genes. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR).
Time FrameFrom randomization to disease progression (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Number [Percentage of participants]
6.2
1.7%
22.3
6.4%
6. Secondary Outcome
TitleOverall Survival (OS)
DescriptionOverall Survival (OS) was defined as the number of days the date of randomization to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.
Time FrameFrom randomization to death (up to approximately 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Median (95% Confidence Interval) [Months]
NA
NA
7. Secondary Outcome
TitleProgression Free Survival on Next Line of Therapy (PFS2)
DescriptionProgression-free survival after next-line therapy is defined as the time from randomization to progression on the next line of subsequent antimyeloma therapy or death due to any cause (prior to start of second line of antimyeloma therapy), whichever comes first. Disease progression on next line of treatment was based on investigator judgment.
Time FrameFrom randomization to either disease progression or death whichever occurs first (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Median (95% Confidence Interval) [Months]
NA
NA
8. Secondary Outcome
TitlePercentage of Participants With Stringent Complete Response (sCR)
DescriptionsCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. CR: Negative immunofixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; <5% plasma cells (PCs) in bone marrow.
Time FrameFrom randomization to disease progression (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Number [Percentage of participants]
9.3
2.6%
20.3
5.8%
9. Secondary Outcome
TitleTime to Disease Progression (TTP)
DescriptionTTP: Time from date of randomization to date of first documented evidence of PD or death due to PD, whichever occurs first. PD per IMWG criteria- Increase of 25 % from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase >10 milligram per deciliter [mg/dL]); Only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cells (PC)% (absolute % >=10%); Bone marrow PC %: absolute % >10%; Definite development of new bone lesions/soft tissue plasmacytomas or 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.
Time FrameFrom randomization to either disease progression or death due to PD whichever occurs first (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Median (95% Confidence Interval) [Months]
19.35
NA
10. Secondary Outcome
TitleTime to Response
DescriptionTime to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%.
Time FrameFrom randomization to first documented PR or better (up to 2.4 years)

Outcome Measure Data

Analysis Population Description
Response-evaluable population: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening, must receive at least one component of study treatment and have adequate post-baseline disease assessments. "N" (number of participants analyzed) signifies number of participants evaluable for this endpoint.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants263318
Median (95% Confidence Interval) [Months]
0.82
0.79
11. Secondary Outcome
TitleDuration of Response (DOR)
DescriptionDOR: participants with a confirmed response (PR or better) as time between first documentation of response and disease progression, IMWG response criteria, or death due to PD, whichever occurs first. PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase>=0.5 g/dL); Urine M-component (absolute increase>=200 mg/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); Only participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC%(absolute%>=10%); Bone marrow PC's %: absolute%>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in the size of existing bone lesions or soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time FrameUp to 2.4 years

Outcome Measure Data

Analysis Population Description
Response-evaluable set: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must have received at least one component of study treatment and have adequate post-baseline disease assessments. "N"(number of participants analyzed) signifies number of participants evaluable for this endpoint.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants263318
Median (95% Confidence Interval) [Months]
21.3
NA
12. Secondary Outcome
TitleTime to Next Treatment (TNT)
DescriptionTime to next treatment is defined as the time from randomization to the start of the next-line treatment.
Time FrameApproximately up to 2.4 years

Outcome Measure Data

Analysis Population Description
ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants356350
Median (95% Confidence Interval) [Months]
NA
NA
13. Secondary Outcome
TitlePercentage of Participants With Best M-protein Response
DescriptionPercentage of participants with Best M- protein response of 100% reduction and >=90% to < 100% reduction were assessed. Best M-protein response was defined as the maximal percent reduction or the lowest percent increase from baseline in serum M-protein for participants with measurable heavy chain at baseline or urine M-protein for participants without measurable heavy chain, but with measurable light chain disease at baseline. For participants without measurable heavy chain and light chain disease at baseline, best response in serum free light chain (FLC) was defined as the maximal percent reduction or the lowest percent increase from baseline in the difference between involved and uninvolved serum FLC level (dFLC).
Time FrameApproximately up to 2.4 years

Outcome Measure Data

Analysis Population Description
Response-evaluable set: participants have confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must receive at least one component of study treatment, have adequate post-baseline disease assessments. 'n' (number of participants analyzed) signifies number of participants analyzed for each specified category.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants341337
Best M-protein response in serum: 100% reduction
38.7
10.9%
58.5
16.7%
Best M-protein response in serum:>= 90 to < 100%
14.6
4.1%
15.2
4.3%
Best M-protein response in urine:100% reduction
69.4
19.5%
90.5
25.9%
Best M-protein response in urine:>=90 to < 100%
13.9
3.9%
7.1
2%
Best response in dFLC:100% reduction
0
0%
0
0%
Best response in dFLC: >=90% to < 100% reduction
77.8
21.9%
100.0
28.6%
14. Secondary Outcome
TitleChange From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score
DescriptionThe EORTC QLQ-C30 is a 30 items self-reporting questionnaire, with a 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores are transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values indicate deterioration in quality of life or functioning and positive values indicate improvement.
Time FrameBaseline, Months 3, 6, 9, 12 and 18

Outcome Measure Data

Analysis Population Description
ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants327316
Month 3
9.4
8.8
Month 6
10.5
10.6
Month 9
11.9
11.1
Month 12
11
12.6
Month 18
12.7
11.4
15. Secondary Outcome
TitleChange From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS)
DescriptionEQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time FrameBaseline, Months 3, 6, 9, 12 and 18

Outcome Measure Data

Analysis Population Description
ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants325315
Baseline
60.33
(20.610)
57.90
(20.190)
Month 3
4.20
(18.417)
9.28
(20.195)
Month 6
7.40
(18.002)
10.83
(20.123)
Month 9
9.89
(19.516)
12.50
(20.616)
Month 12
10.80
(19.386)
10.79
(20.271)
Month 18
7.65
(19.284)
12.04
(20.126)
16. Secondary Outcome
TitleChange From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score
DescriptionEQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.
Time FrameBaseline, Months 3, 6, 9, 12 and 18

Outcome Measure Data

Analysis Population Description
ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
Measure Participants325315
Baseline
0.59
(0.301)
0.57
(0.292)
Month 3
0.09
(0.312)
0.12
(0.265)
Month 6
0.12
(0.270)
0.13
(0.271)
Month 9
0.16
(0.270)
0.16
(0.270)
Month 12
0.15
(0.278)
0.17
(0.287)
Month 18
0.13
(0.247)
0.13
(0.314)

Adverse Events

Time FrameUp to 2.4 years
Adverse Event Reporting Description Safety population defined as participants who have received at least 1 administration of any study drug.
Arm/Group TitleVelcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Arm/Group DescriptionParticipants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (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 to 4 and prednisone 60 mg/m^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.Participants received 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 to 4 and prednisone 60 mg/m^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (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 study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.
All Cause Mortality
Velcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total48/354 (13.6%) 45/346 (13%)
Serious Adverse Events
Velcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total115/354 (32.5%) 144/346 (41.6%)
Blood and lymphatic system disorders
Anaemia9/354 (2.5%) 6/346 (1.7%)
Febrile Neutropenia7/354 (2%) 2/346 (0.6%)
Leukopenia1/354 (0.3%) 0/346 (0%)
Neutropenia4/354 (1.1%) 3/346 (0.9%)
Thrombocytopenia4/354 (1.1%) 5/346 (1.4%)
Cardiac disorders
Acute Coronary Syndrome1/354 (0.3%) 1/346 (0.3%)
Acute Myocardial Infarction0/354 (0%) 2/346 (0.6%)
Angina Unstable1/354 (0.3%) 0/346 (0%)
Atrial Fibrillation2/354 (0.6%) 6/346 (1.7%)
Cardiac Arrest2/354 (0.6%) 1/346 (0.3%)
Cardiac Failure7/354 (2%) 1/346 (0.3%)
Cardiac Failure Acute0/354 (0%) 1/346 (0.3%)
Cardiac Failure Chronic0/354 (0%) 1/346 (0.3%)
Cardiac Failure Congestive0/354 (0%) 1/346 (0.3%)
Cardio-Respiratory Arrest1/354 (0.3%) 0/346 (0%)
Cardiovascular Insufficiency0/354 (0%) 1/346 (0.3%)
Sinus Bradycardia0/354 (0%) 2/346 (0.6%)
Stress Cardiomyopathy0/354 (0%) 1/346 (0.3%)
Supraventricular Tachycardia1/354 (0.3%) 1/346 (0.3%)
Tachycardia0/354 (0%) 1/346 (0.3%)
Eye disorders
Conjunctival Haemorrhage0/354 (0%) 1/346 (0.3%)
Retinal Detachment0/354 (0%) 1/346 (0.3%)
Gastrointestinal disorders
Abdominal Adhesions0/354 (0%) 1/346 (0.3%)
Abdominal Pain0/354 (0%) 1/346 (0.3%)
Abdominal Pain Upper1/354 (0.3%) 0/346 (0%)
Anal Haemorrhage0/354 (0%) 1/346 (0.3%)
Colitis1/354 (0.3%) 0/346 (0%)
Constipation1/354 (0.3%) 0/346 (0%)
Diarrhoea2/354 (0.6%) 2/346 (0.6%)
Diverticular Perforation1/354 (0.3%) 0/346 (0%)
Enterocolitis0/354 (0%) 1/346 (0.3%)
Gastric Haemorrhage1/354 (0.3%) 0/346 (0%)
Gastritis1/354 (0.3%) 0/346 (0%)
Gastrointestinal Disorder1/354 (0.3%) 0/346 (0%)
Gastrointestinal Haemorrhage0/354 (0%) 2/346 (0.6%)
Haematemesis2/354 (0.6%) 0/346 (0%)
Haemorrhoidal Haemorrhage0/354 (0%) 1/346 (0.3%)
Ileus1/354 (0.3%) 0/346 (0%)
Ileus Paralytic1/354 (0.3%) 1/346 (0.3%)
Inguinal Hernia0/354 (0%) 1/346 (0.3%)
Large Intestine Perforation0/354 (0%) 1/346 (0.3%)
Nausea1/354 (0.3%) 0/346 (0%)
Oesophageal Rupture1/354 (0.3%) 0/346 (0%)
Oesophagitis Haemorrhagic1/354 (0.3%) 0/346 (0%)
Rectal Haemorrhage1/354 (0.3%) 1/346 (0.3%)
Vomiting6/354 (1.7%) 2/346 (0.6%)
General disorders
Asthenia2/354 (0.6%) 2/346 (0.6%)
Chest Pain0/354 (0%) 1/346 (0.3%)
Death2/354 (0.6%) 2/346 (0.6%)
Fatigue2/354 (0.6%) 1/346 (0.3%)
Generalised Oedema0/354 (0%) 1/346 (0.3%)
Hyperthermia0/354 (0%) 1/346 (0.3%)
Malaise1/354 (0.3%) 0/346 (0%)
Multiple Organ Dysfunction Syndrome1/354 (0.3%) 0/346 (0%)
Non-Cardiac Chest Pain2/354 (0.6%) 1/346 (0.3%)
Pain1/354 (0.3%) 1/346 (0.3%)
Pyrexia5/354 (1.4%) 5/346 (1.4%)
Hepatobiliary disorders
Cholelithiasis1/354 (0.3%) 0/346 (0%)
Infections and infestations
Abdominal Abscess1/354 (0.3%) 0/346 (0%)
Bacteraemia0/354 (0%) 2/346 (0.6%)
Bronchitis2/354 (0.6%) 8/346 (2.3%)
Candida Sepsis1/354 (0.3%) 0/346 (0%)
Cellulitis1/354 (0.3%) 0/346 (0%)
Clostridium Colitis1/354 (0.3%) 1/346 (0.3%)
Clostridium Difficile Colitis1/354 (0.3%) 0/346 (0%)
Clostridium Difficile Infection2/354 (0.6%) 0/346 (0%)
Cytomegalovirus Infection0/354 (0%) 2/346 (0.6%)
Device Related Infection1/354 (0.3%) 0/346 (0%)
Diverticulitis0/354 (0%) 1/346 (0.3%)
Enterococcal Bacteraemia1/354 (0.3%) 0/346 (0%)
Epiglottitis0/354 (0%) 1/346 (0.3%)
Gastroenteritis2/354 (0.6%) 1/346 (0.3%)
H1n1 Influenza0/354 (0%) 1/346 (0.3%)
Herpes Zoster1/354 (0.3%) 0/346 (0%)
Herpes Zoster Disseminated0/354 (0%) 1/346 (0.3%)
Infection1/354 (0.3%) 3/346 (0.9%)
Infective Exacerbation of Chronic Obstructive Airways Disease1/354 (0.3%) 0/346 (0%)
Infective Myositis0/354 (0%) 1/346 (0.3%)
Influenza2/354 (0.6%) 3/346 (0.9%)
Lower Respiratory Tract Infection3/354 (0.8%) 8/346 (2.3%)
Lower Respiratory Tract Infection Bacterial0/354 (0%) 1/346 (0.3%)
Lung Infection1/354 (0.3%) 1/346 (0.3%)
Meningitis Pneumococcal0/354 (0%) 1/346 (0.3%)
Neutropenic Infection1/354 (0.3%) 1/346 (0.3%)
Pelvic Infection1/354 (0.3%) 0/346 (0%)
Peritonitis0/354 (0%) 1/346 (0.3%)
Pharyngitis0/354 (0%) 1/346 (0.3%)
Pneumococcal Sepsis0/354 (0%) 1/346 (0.3%)
Pneumonia11/354 (3.1%) 35/346 (10.1%)
Pneumonia Bacterial1/354 (0.3%) 0/346 (0%)
Pneumonia Pneumococcal0/354 (0%) 2/346 (0.6%)
Pneumonia Streptococcal1/354 (0.3%) 0/346 (0%)
Pneumonia Viral0/354 (0%) 1/346 (0.3%)
Pseudomembranous Colitis0/354 (0%) 1/346 (0.3%)
Pulmonary Sepsis1/354 (0.3%) 0/346 (0%)
Respiratory Syncytial Virus Infection0/354 (0%) 1/346 (0.3%)
Respiratory Tract Infection0/354 (0%) 2/346 (0.6%)
Sepsis5/354 (1.4%) 5/346 (1.4%)
Septic Shock2/354 (0.6%) 1/346 (0.3%)
Staphylococcal Infection1/354 (0.3%) 0/346 (0%)
Tuberculosis0/354 (0%) 1/346 (0.3%)
Tuberculous Pleurisy1/354 (0.3%) 0/346 (0%)
Upper Respiratory Tract Infection3/354 (0.8%) 7/346 (2%)
Urinary Tract Infection1/354 (0.3%) 4/346 (1.2%)
Urinary Tract Infection Bacterial1/354 (0.3%) 1/346 (0.3%)
Urosepsis0/354 (0%) 1/346 (0.3%)
Wound Infection0/354 (0%) 1/346 (0.3%)
Injury, poisoning and procedural complications
Chest Injury0/354 (0%) 1/346 (0.3%)
Femoral Neck Fracture1/354 (0.3%) 0/346 (0%)
Femur Fracture2/354 (0.6%) 4/346 (1.2%)
Foot Fracture0/354 (0%) 1/346 (0.3%)
Humerus Fracture2/354 (0.6%) 0/346 (0%)
Infusion Related Reaction0/354 (0%) 1/346 (0.3%)
Skeletal Injury1/354 (0.3%) 0/346 (0%)
Spinal Compression Fracture1/354 (0.3%) 4/346 (1.2%)
Subarachnoid Haemorrhage0/354 (0%) 1/346 (0.3%)
Toxicity to Various Agents0/354 (0%) 1/346 (0.3%)
Traumatic Shock1/354 (0.3%) 0/346 (0%)
Upper Limb Fracture0/354 (0%) 1/346 (0.3%)
Wrist Fracture1/354 (0.3%) 0/346 (0%)
Investigations
Alanine Aminotransferase Increased1/354 (0.3%) 0/346 (0%)
Aspartate Aminotransferase Increased2/354 (0.6%) 0/346 (0%)
Blood Creatinine Increased1/354 (0.3%) 1/346 (0.3%)
C-Reactive Protein Increased0/354 (0%) 1/346 (0.3%)
Oxygen Saturation Decreased0/354 (0%) 2/346 (0.6%)
Troponin Increased1/354 (0.3%) 0/346 (0%)
Metabolism and nutrition disorders
Decreased Appetite0/354 (0%) 1/346 (0.3%)
Dehydration1/354 (0.3%) 2/346 (0.6%)
Hyperkalaemia1/354 (0.3%) 0/346 (0%)
Hypophagia0/354 (0%) 1/346 (0.3%)
Tumour Lysis Syndrome1/354 (0.3%) 1/346 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia0/354 (0%) 1/346 (0.3%)
Back Pain3/354 (0.8%) 6/346 (1.7%)
Bone Pain1/354 (0.3%) 2/346 (0.6%)
Dactylitis0/354 (0%) 1/346 (0.3%)
Neck Pain0/354 (0%) 1/346 (0.3%)
Osteonecrosis1/354 (0.3%) 0/346 (0%)
Spinal Column Stenosis0/354 (0%) 1/346 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia1/354 (0.3%) 0/346 (0%)
Adenocarcinoma of Colon1/354 (0.3%) 0/346 (0%)
Bile Duct Cancer0/354 (0%) 1/346 (0.3%)
Breast Cancer1/354 (0.3%) 0/346 (0%)
Meningioma1/354 (0.3%) 0/346 (0%)
Oesophageal Adenocarcinoma0/354 (0%) 1/346 (0.3%)
Plasmacytoma0/354 (0%) 1/346 (0.3%)
Rectal Adenocarcinoma1/354 (0.3%) 0/346 (0%)
Renal Cell Carcinoma0/354 (0%) 1/346 (0.3%)
Nervous system disorders
Autonomic Nervous System Imbalance1/354 (0.3%) 0/346 (0%)
Cerebral Infarction1/354 (0.3%) 0/346 (0%)
Cerebral Ischaemia1/354 (0.3%) 0/346 (0%)
Cerebrovascular Accident0/354 (0%) 1/346 (0.3%)
Dizziness1/354 (0.3%) 0/346 (0%)
Epilepsy0/354 (0%) 1/346 (0.3%)
Haemorrhage Intracranial0/354 (0%) 1/346 (0.3%)
Headache2/354 (0.6%) 0/346 (0%)
Ischaemic Stroke1/354 (0.3%) 2/346 (0.6%)
Neuralgia0/354 (0%) 1/346 (0.3%)
Neurotoxicity1/354 (0.3%) 0/346 (0%)
Paraesthesia1/354 (0.3%) 1/346 (0.3%)
Paraparesis0/354 (0%) 1/346 (0.3%)
Parkinson's Disease0/354 (0%) 1/346 (0.3%)
Peripheral Motor Neuropathy0/354 (0%) 1/346 (0.3%)
Peripheral Sensorimotor Neuropathy0/354 (0%) 1/346 (0.3%)
Peripheral Sensory Neuropathy2/354 (0.6%) 2/346 (0.6%)
Sciatica0/354 (0%) 1/346 (0.3%)
Somnolence0/354 (0%) 1/346 (0.3%)
Spinal Cord Compression0/354 (0%) 1/346 (0.3%)
Syncope0/354 (0%) 1/346 (0.3%)
Psychiatric disorders
Agitation0/354 (0%) 1/346 (0.3%)
Delirium1/354 (0.3%) 0/346 (0%)
Depression1/354 (0.3%) 1/346 (0.3%)
Psychotic Disorder1/354 (0.3%) 0/346 (0%)
Renal and urinary disorders
Acute Kidney Injury5/354 (1.4%) 3/346 (0.9%)
Anuria1/354 (0.3%) 0/346 (0%)
Chronic Kidney Disease1/354 (0.3%) 0/346 (0%)
Haematuria0/354 (0%) 1/346 (0.3%)
Prerenal Failure1/354 (0.3%) 0/346 (0%)
Renal Failure1/354 (0.3%) 1/346 (0.3%)
Urinary Retention1/354 (0.3%) 0/346 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome0/354 (0%) 1/346 (0.3%)
Acute Respiratory Failure0/354 (0%) 2/346 (0.6%)
Bronchiectasis0/354 (0%) 1/346 (0.3%)
Bronchospasm0/354 (0%) 2/346 (0.6%)
Chronic Obstructive Pulmonary Disease0/354 (0%) 1/346 (0.3%)
Cough0/354 (0%) 1/346 (0.3%)
Dyspnoea4/354 (1.1%) 6/346 (1.7%)
Haemoptysis1/354 (0.3%) 0/346 (0%)
Hypoxia0/354 (0%) 2/346 (0.6%)
Interstitial Lung Disease0/354 (0%) 1/346 (0.3%)
Laryngeal Oedema1/354 (0.3%) 0/346 (0%)
Obstructive Airways Disorder1/354 (0.3%) 0/346 (0%)
Pneumonitis0/354 (0%) 1/346 (0.3%)
Pneumothorax Spontaneous1/354 (0.3%) 0/346 (0%)
Pulmonary Embolism4/354 (1.1%) 0/346 (0%)
Pulmonary Oedema0/354 (0%) 6/346 (1.7%)
Tachypnoea0/354 (0%) 1/346 (0.3%)
Wheezing0/354 (0%) 1/346 (0.3%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer0/354 (0%) 1/346 (0.3%)
Erythema Multiforme2/354 (0.6%) 0/346 (0%)
Rash Erythematous0/354 (0%) 1/346 (0.3%)
Rash Vesicular1/354 (0.3%) 0/346 (0%)
Vascular disorders
Hypertension1/354 (0.3%) 2/346 (0.6%)
Hypotension1/354 (0.3%) 1/346 (0.3%)
Hypovolaemic Shock0/354 (0%) 1/346 (0.3%)
Orthostatic Hypotension0/354 (0%) 1/346 (0.3%)
Thrombophlebitis2/354 (0.6%) 0/346 (0%)
Other (Not Including Serious) Adverse Events
Velcade, Melphalan and Prednisone (VMP)Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total331/354 (93.5%) 324/346 (93.6%)
Blood and lymphatic system disorders
Anaemia131/354 (37%) 94/346 (27.2%)
Leukopenia53/354 (15%) 46/346 (13.3%)
Lymphopenia36/354 (10.2%) 37/346 (10.7%)
Neutropenia186/354 (52.5%) 171/346 (49.4%)
Thrombocytopenia189/354 (53.4%) 168/346 (48.6%)
Gastrointestinal disorders
Abdominal Pain25/354 (7.1%) 18/346 (5.2%)
Constipation64/354 (18.1%) 63/346 (18.2%)
Diarrhoea87/354 (24.6%) 81/346 (23.4%)
Dyspepsia12/354 (3.4%) 18/346 (5.2%)
Nausea76/354 (21.5%) 72/346 (20.8%)
Vomiting52/354 (14.7%) 59/346 (17.1%)
General disorders
Asthenia42/354 (11.9%) 40/346 (11.6%)
Chills6/354 (1.7%) 26/346 (7.5%)
Fatigue50/354 (14.1%) 47/346 (13.6%)
Injection Site Erythema28/354 (7.9%) 12/346 (3.5%)
Oedema Peripheral39/354 (11%) 62/346 (17.9%)
Pyrexia70/354 (19.8%) 78/346 (22.5%)
Infections and infestations
Bronchitis25/354 (7.1%) 44/346 (12.7%)
Nasopharyngitis20/354 (5.6%) 19/346 (5.5%)
Pneumonia7/354 (2%) 25/346 (7.2%)
Upper Respiratory Tract Infection48/354 (13.6%) 87/346 (25.1%)
Urinary Tract Infection12/354 (3.4%) 26/346 (7.5%)
Metabolism and nutrition disorders
Decreased Appetite46/354 (13%) 40/346 (11.6%)
Hyperglycaemia13/354 (3.7%) 21/346 (6.1%)
Hypocalcaemia17/354 (4.8%) 20/346 (5.8%)
Hypokalaemia17/354 (4.8%) 19/346 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia22/354 (6.2%) 26/346 (7.5%)
Back Pain40/354 (11.3%) 42/346 (12.1%)
Bone Pain8/354 (2.3%) 19/346 (5.5%)
Pain in Extremity22/354 (6.2%) 29/346 (8.4%)
Nervous system disorders
Dizziness21/354 (5.9%) 22/346 (6.4%)
Headache12/354 (3.4%) 23/346 (6.6%)
Neuralgia16/354 (4.5%) 24/346 (6.9%)
Paraesthesia19/354 (5.4%) 15/346 (4.3%)
Peripheral Sensory Neuropathy121/354 (34.2%) 98/346 (28.3%)
Psychiatric disorders
Insomnia32/354 (9%) 26/346 (7.5%)
Respiratory, thoracic and mediastinal disorders
Cough27/354 (7.6%) 51/346 (14.7%)
Dyspnoea14/354 (4%) 39/346 (11.3%)
Skin and subcutaneous tissue disorders
Pruritus10/354 (2.8%) 19/346 (5.5%)
Rash39/354 (11%) 29/346 (8.4%)
Vascular disorders
Hypertension10/354 (2.8%) 33/346 (9.5%)
Hypotension23/354 (6.5%) 30/346 (8.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.

Results Point of Contact

Name/TitleExecutive Medical Director
OrganizationJanssen Research and Development, LLC
Phone844-434-4210
EmailClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02195479
Other Study ID Numbers:
  • CR104761
  • 54767414MMY3007
  • 2014-002272-88
First Posted:
Jul 21, 2014
Last Update Posted:
Dec 3, 2021
Last Verified:
Dec 1, 2021