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
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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
Arms and Interventions
| Arm | Intervention/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
- 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
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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%.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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
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
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A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
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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
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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
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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)
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Participants with known or suspected COPD must have a FEV1 test during screening
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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
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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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | California City | California | United States | ||
| 2 | Corona | California | United States | ||
| 3 | Fountain Valley | California | United States | ||
| 4 | Los Angeles | California | United States | ||
| 5 | Hialeah | Florida | United States | ||
| 6 | Orange Park | Florida | United States | ||
| 7 | Chicago | Illinois | United States | ||
| 8 | Springfield | Missouri | United States | ||
| 9 | Cleveland | Ohio | United States | ||
| 10 | Fredericksburg | Virginia | United States | ||
| 11 | Buenos Aires | Argentina | |||
| 12 | Ciudad Autonoma Buenos Aires | Argentina | |||
| 13 | Córdoba | Argentina | |||
| 14 | Santa Fe | Argentina | |||
| 15 | Adelaide | Australia | |||
| 16 | Bendigo | Australia | |||
| 17 | Camperdown N/a | Australia | |||
| 18 | Geelong | Australia | |||
| 19 | Gosford | Australia | |||
| 20 | Greenslopes | Australia | |||
| 21 | Hobart | Australia | |||
| 22 | North Adelaide | Australia | |||
| 23 | Parkville | Australia | |||
| 24 | Antwerpen | Belgium | |||
| 25 | Antwerp | Belgium | |||
| 26 | Brussel | Belgium | |||
| 27 | Charleroi | Belgium | |||
| 28 | Gent | Belgium | |||
| 29 | Kortrijk | Belgium | |||
| 30 | Roeselare | Belgium | |||
| 31 | Turnhout | Belgium | |||
| 32 | Yvoir | Belgium | |||
| 33 | Barretos | Brazil | |||
| 34 | Cuiaba - Mount | Brazil | |||
| 35 | Fortaleza Ceara | Brazil | |||
| 36 | Fortaleza | Brazil | |||
| 37 | Goiânia | Brazil | |||
| 38 | Natal | Brazil | |||
| 39 | Niteroi N/a | Brazil | |||
| 40 | Porto Alegre | Brazil | |||
| 41 | Riberao Preto | Brazil | |||
| 42 | Sao Paulo | Brazil | |||
| 43 | Pleven | Bulgaria | |||
| 44 | Plovdiv | Bulgaria | |||
| 45 | Sofia | Bulgaria | |||
| 46 | Varna | Bulgaria | |||
| 47 | Vratsa | Bulgaria | |||
| 48 | Zadar | Croatia | |||
| 49 | Zagreb | Croatia | |||
| 50 | Brno | Czechia | |||
| 51 | Hradec Kralove | Czechia | |||
| 52 | Olomouc | Czechia | |||
| 53 | Ostrava-Poruba | Czechia | |||
| 54 | Praha 10 | Czechia | |||
| 55 | Praha 2 | Czechia | |||
| 56 | Tbilisi | Georgia | |||
| 57 | Berlin | Germany | |||
| 58 | Dortmund | Germany | |||
| 59 | Karlsruhe | Germany | |||
| 60 | Potsdam | Germany | |||
| 61 | Saarbrücken | Germany | |||
| 62 | Stuttgart | Germany | |||
| 63 | Würzburg | Germany | |||
| 64 | Athens Attica | Greece | |||
| 65 | Athens | Greece | |||
| 66 | Patra | Greece | |||
| 67 | Thessaloniki | Greece | |||
| 68 | Budapest | Hungary | |||
| 69 | Debrecen | Hungary | |||
| 70 | Kaposvar | Hungary | |||
| 71 | Pecs N/a | Hungary | |||
| 72 | Chiba | Japan | |||
| 73 | Hitachi | Japan | |||
| 74 | Kanazawa | Japan | |||
| 75 | Kawasaki | Japan | |||
| 76 | Kobe | Japan | |||
| 77 | Kurume | Japan | |||
| 78 | Matsuyama | Japan | |||
| 79 | Nagoya | Japan | |||
| 80 | Narita | Japan | |||
| 81 | Ohgaki | Japan | |||
| 82 | Okayama | Japan | |||
| 83 | Osaka | Japan | |||
| 84 | Sendai-shi | Japan | |||
| 85 | Shibukawa | Japan | |||
| 86 | Shibuya | Japan | |||
| 87 | Tachikawa | Japan | |||
| 88 | Toyohashi | Japan | |||
| 89 | Busan | Korea, Republic of | |||
| 90 | Gyeonggi-do | Korea, Republic of | |||
| 91 | Hwasun | Korea, Republic of | |||
| 92 | Incheon | Korea, Republic of | |||
| 93 | Seongnam | Korea, Republic of | |||
| 94 | Seoul | Korea, Republic of | |||
| 95 | Skopje | North Macedonia | |||
| 96 | Bialystok | Poland | |||
| 97 | Bydgoszcz | Poland | |||
| 98 | Chorzow | Poland | |||
| 99 | Gdansk | Poland | |||
| 100 | Legnica | Poland | |||
| 101 | Lublin | Poland | |||
| 102 | Opole | Poland | |||
| 103 | Slupsk | Poland | |||
| 104 | Warszawa Ul | Poland | |||
| 105 | Warszawa | Poland | |||
| 106 | Wroclaw | Poland | |||
| 107 | Lisboa | Portugal | |||
| 108 | Lisbon | Portugal | |||
| 109 | Porto | Portugal | |||
| 110 | Brasov | Romania | |||
| 111 | Bucharest | Romania | |||
| 112 | Iasi | Romania | |||
| 113 | Arkhangelsk | Russian Federation | |||
| 114 | Dzerzhinsk | Russian Federation | |||
| 115 | Ekaterinbourg | Russian Federation | |||
| 116 | Nizhny Novgorod | Russian Federation | |||
| 117 | Ryazan | Russian Federation | |||
| 118 | Saint-Petersburg | Russian Federation | |||
| 119 | Saratov | Russian Federation | |||
| 120 | Sochi | Russian Federation | |||
| 121 | St Petersburg | Russian Federation | |||
| 122 | Volgograd | Russian Federation | |||
| 123 | Belgrade | Serbia | |||
| 124 | Nis | Serbia | |||
| 125 | Novi Sad | Serbia | |||
| 126 | Sremska Kamenica | Serbia | |||
| 127 | Zemun | Serbia | |||
| 128 | Andalucía | Spain | |||
| 129 | Badalona | Spain | |||
| 130 | Barcelona | Spain | |||
| 131 | Córdoba | Spain | |||
| 132 | Girona | Spain | |||
| 133 | La Laguna | Spain | |||
| 134 | Madrid | Spain | |||
| 135 | Maranon | Spain | |||
| 136 | Murcia N/a | Spain | |||
| 137 | Ourense | Spain | |||
| 138 | Pamplona | Spain | |||
| 139 | Salamanca | Spain | |||
| 140 | Sevilla | Spain | |||
| 141 | Toledo | Spain | |||
| 142 | Valencia | Spain | |||
| 143 | Zaragoza | Spain | |||
| 144 | Altindag | Turkey | |||
| 145 | Ankara | Turkey | |||
| 146 | Aydin | Turkey | |||
| 147 | Izmir | Turkey | |||
| 148 | Kayseri | Turkey | |||
| 149 | Samsun | Turkey | |||
| 150 | Tekirdag | Turkey | |||
| 151 | Cherkassy | Ukraine | |||
| 152 | Dnepropetrovsk | Ukraine | |||
| 153 | Ivano-Frankivsk | Ukraine | |||
| 154 | Kharkov | Ukraine | |||
| 155 | Khmelnitskiy | Ukraine | |||
| 156 | Lviv | Ukraine | |||
| 157 | Zaporizhzhia | Ukraine | |||
| 158 | Birmingham | United Kingdom | |||
| 159 | Cambridge | United Kingdom | |||
| 160 | Colchester | United Kingdom | |||
| 161 | Harlow | United Kingdom | |||
| 162 | Leicester | United Kingdom | |||
| 163 | London | United Kingdom | |||
| 164 | Manchester | United Kingdom | |||
| 165 | Woolwich | United 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.- CR104761
- 54767414MMY3007
- 2014-002272-88
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Results 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 | ||
| STARTED | 356 | 350 |
| Treated | 354 | 346 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 356 | 350 |
Baseline Characteristics
| Arm/Group Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) | Total |
|---|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 | 706 |
| 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
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Median (95% Confidence Interval) [Months] |
18.14
|
NA
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Number [Percentage of participants] |
73.9
20.8%
|
90.9
26%
|
| Title | Percentage of Participants With Very Good Partial Response (VGPR) or Better |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Number [Percentage of participants] |
49.7
14%
|
71.1
20.3%
|
| Title | Percentage of Participants With Complete Response (CR) or Better |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Number [Percentage of participants] |
24.4
6.9%
|
42.6
12.2%
|
| Title | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
|---|---|
| Description | 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). |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Number [Percentage of participants] |
6.2
1.7%
|
22.3
6.4%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
| Title | Progression Free Survival on Next Line of Therapy (PFS2) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
| Title | Percentage of Participants With Stringent Complete Response (sCR) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Number [Percentage of participants] |
9.3
2.6%
|
20.3
5.8%
|
| Title | Time to Disease Progression (TTP) |
|---|---|
| Description | 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. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Median (95% Confidence Interval) [Months] |
19.35
|
NA
|
| Title | Time to Response |
|---|---|
| Description | 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%. |
| Time Frame | From 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 263 | 318 |
| Median (95% Confidence Interval) [Months] |
0.82
|
0.79
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | 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. |
| Time Frame | Up 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 263 | 318 |
| Median (95% Confidence Interval) [Months] |
21.3
|
NA
|
| Title | Time to Next Treatment (TNT) |
|---|---|
| Description | Time to next treatment is defined as the time from randomization to the start of the next-line treatment. |
| Time Frame | Approximately 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 356 | 350 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
| Title | Percentage of Participants With Best M-protein Response |
|---|---|
| Description | 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). |
| Time Frame | Approximately 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 341 | 337 |
| 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%
|
| Title | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline, 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 327 | 316 |
| 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
|
| Title | Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 325 | 315 |
| 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)
|
| Title | Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline, 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) |
|---|---|---|
| Arm/Group Description | Participants 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 Participants | 325 | 315 |
| 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 Frame | Up 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 Title | Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) | ||
| Arm/Group Description | Participants 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/354 (13.6%) | 45/346 (13%) | ||
Serious Adverse Events |
||||
| Velcade, Melphalan and Prednisone (VMP) | Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 115/354 (32.5%) | 144/346 (41.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 9/354 (2.5%) | 6/346 (1.7%) | ||
| Febrile Neutropenia | 7/354 (2%) | 2/346 (0.6%) | ||
| Leukopenia | 1/354 (0.3%) | 0/346 (0%) | ||
| Neutropenia | 4/354 (1.1%) | 3/346 (0.9%) | ||
| Thrombocytopenia | 4/354 (1.1%) | 5/346 (1.4%) | ||
| Cardiac disorders | ||||
| Acute Coronary Syndrome | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Acute Myocardial Infarction | 0/354 (0%) | 2/346 (0.6%) | ||
| Angina Unstable | 1/354 (0.3%) | 0/346 (0%) | ||
| Atrial Fibrillation | 2/354 (0.6%) | 6/346 (1.7%) | ||
| Cardiac Arrest | 2/354 (0.6%) | 1/346 (0.3%) | ||
| Cardiac Failure | 7/354 (2%) | 1/346 (0.3%) | ||
| Cardiac Failure Acute | 0/354 (0%) | 1/346 (0.3%) | ||
| Cardiac Failure Chronic | 0/354 (0%) | 1/346 (0.3%) | ||
| Cardiac Failure Congestive | 0/354 (0%) | 1/346 (0.3%) | ||
| Cardio-Respiratory Arrest | 1/354 (0.3%) | 0/346 (0%) | ||
| Cardiovascular Insufficiency | 0/354 (0%) | 1/346 (0.3%) | ||
| Sinus Bradycardia | 0/354 (0%) | 2/346 (0.6%) | ||
| Stress Cardiomyopathy | 0/354 (0%) | 1/346 (0.3%) | ||
| Supraventricular Tachycardia | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Tachycardia | 0/354 (0%) | 1/346 (0.3%) | ||
| Eye disorders | ||||
| Conjunctival Haemorrhage | 0/354 (0%) | 1/346 (0.3%) | ||
| Retinal Detachment | 0/354 (0%) | 1/346 (0.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Adhesions | 0/354 (0%) | 1/346 (0.3%) | ||
| Abdominal Pain | 0/354 (0%) | 1/346 (0.3%) | ||
| Abdominal Pain Upper | 1/354 (0.3%) | 0/346 (0%) | ||
| Anal Haemorrhage | 0/354 (0%) | 1/346 (0.3%) | ||
| Colitis | 1/354 (0.3%) | 0/346 (0%) | ||
| Constipation | 1/354 (0.3%) | 0/346 (0%) | ||
| Diarrhoea | 2/354 (0.6%) | 2/346 (0.6%) | ||
| Diverticular Perforation | 1/354 (0.3%) | 0/346 (0%) | ||
| Enterocolitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Gastric Haemorrhage | 1/354 (0.3%) | 0/346 (0%) | ||
| Gastritis | 1/354 (0.3%) | 0/346 (0%) | ||
| Gastrointestinal Disorder | 1/354 (0.3%) | 0/346 (0%) | ||
| Gastrointestinal Haemorrhage | 0/354 (0%) | 2/346 (0.6%) | ||
| Haematemesis | 2/354 (0.6%) | 0/346 (0%) | ||
| Haemorrhoidal Haemorrhage | 0/354 (0%) | 1/346 (0.3%) | ||
| Ileus | 1/354 (0.3%) | 0/346 (0%) | ||
| Ileus Paralytic | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Inguinal Hernia | 0/354 (0%) | 1/346 (0.3%) | ||
| Large Intestine Perforation | 0/354 (0%) | 1/346 (0.3%) | ||
| Nausea | 1/354 (0.3%) | 0/346 (0%) | ||
| Oesophageal Rupture | 1/354 (0.3%) | 0/346 (0%) | ||
| Oesophagitis Haemorrhagic | 1/354 (0.3%) | 0/346 (0%) | ||
| Rectal Haemorrhage | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Vomiting | 6/354 (1.7%) | 2/346 (0.6%) | ||
| General disorders | ||||
| Asthenia | 2/354 (0.6%) | 2/346 (0.6%) | ||
| Chest Pain | 0/354 (0%) | 1/346 (0.3%) | ||
| Death | 2/354 (0.6%) | 2/346 (0.6%) | ||
| Fatigue | 2/354 (0.6%) | 1/346 (0.3%) | ||
| Generalised Oedema | 0/354 (0%) | 1/346 (0.3%) | ||
| Hyperthermia | 0/354 (0%) | 1/346 (0.3%) | ||
| Malaise | 1/354 (0.3%) | 0/346 (0%) | ||
| Multiple Organ Dysfunction Syndrome | 1/354 (0.3%) | 0/346 (0%) | ||
| Non-Cardiac Chest Pain | 2/354 (0.6%) | 1/346 (0.3%) | ||
| Pain | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Pyrexia | 5/354 (1.4%) | 5/346 (1.4%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 1/354 (0.3%) | 0/346 (0%) | ||
| Infections and infestations | ||||
| Abdominal Abscess | 1/354 (0.3%) | 0/346 (0%) | ||
| Bacteraemia | 0/354 (0%) | 2/346 (0.6%) | ||
| Bronchitis | 2/354 (0.6%) | 8/346 (2.3%) | ||
| Candida Sepsis | 1/354 (0.3%) | 0/346 (0%) | ||
| Cellulitis | 1/354 (0.3%) | 0/346 (0%) | ||
| Clostridium Colitis | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Clostridium Difficile Colitis | 1/354 (0.3%) | 0/346 (0%) | ||
| Clostridium Difficile Infection | 2/354 (0.6%) | 0/346 (0%) | ||
| Cytomegalovirus Infection | 0/354 (0%) | 2/346 (0.6%) | ||
| Device Related Infection | 1/354 (0.3%) | 0/346 (0%) | ||
| Diverticulitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Enterococcal Bacteraemia | 1/354 (0.3%) | 0/346 (0%) | ||
| Epiglottitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Gastroenteritis | 2/354 (0.6%) | 1/346 (0.3%) | ||
| H1n1 Influenza | 0/354 (0%) | 1/346 (0.3%) | ||
| Herpes Zoster | 1/354 (0.3%) | 0/346 (0%) | ||
| Herpes Zoster Disseminated | 0/354 (0%) | 1/346 (0.3%) | ||
| Infection | 1/354 (0.3%) | 3/346 (0.9%) | ||
| Infective Exacerbation of Chronic Obstructive Airways Disease | 1/354 (0.3%) | 0/346 (0%) | ||
| Infective Myositis | 0/354 (0%) | 1/346 (0.3%) | ||
| Influenza | 2/354 (0.6%) | 3/346 (0.9%) | ||
| Lower Respiratory Tract Infection | 3/354 (0.8%) | 8/346 (2.3%) | ||
| Lower Respiratory Tract Infection Bacterial | 0/354 (0%) | 1/346 (0.3%) | ||
| Lung Infection | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Meningitis Pneumococcal | 0/354 (0%) | 1/346 (0.3%) | ||
| Neutropenic Infection | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Pelvic Infection | 1/354 (0.3%) | 0/346 (0%) | ||
| Peritonitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Pharyngitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Pneumococcal Sepsis | 0/354 (0%) | 1/346 (0.3%) | ||
| Pneumonia | 11/354 (3.1%) | 35/346 (10.1%) | ||
| Pneumonia Bacterial | 1/354 (0.3%) | 0/346 (0%) | ||
| Pneumonia Pneumococcal | 0/354 (0%) | 2/346 (0.6%) | ||
| Pneumonia Streptococcal | 1/354 (0.3%) | 0/346 (0%) | ||
| Pneumonia Viral | 0/354 (0%) | 1/346 (0.3%) | ||
| Pseudomembranous Colitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Pulmonary Sepsis | 1/354 (0.3%) | 0/346 (0%) | ||
| Respiratory Syncytial Virus Infection | 0/354 (0%) | 1/346 (0.3%) | ||
| Respiratory Tract Infection | 0/354 (0%) | 2/346 (0.6%) | ||
| Sepsis | 5/354 (1.4%) | 5/346 (1.4%) | ||
| Septic Shock | 2/354 (0.6%) | 1/346 (0.3%) | ||
| Staphylococcal Infection | 1/354 (0.3%) | 0/346 (0%) | ||
| Tuberculosis | 0/354 (0%) | 1/346 (0.3%) | ||
| Tuberculous Pleurisy | 1/354 (0.3%) | 0/346 (0%) | ||
| Upper Respiratory Tract Infection | 3/354 (0.8%) | 7/346 (2%) | ||
| Urinary Tract Infection | 1/354 (0.3%) | 4/346 (1.2%) | ||
| Urinary Tract Infection Bacterial | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Urosepsis | 0/354 (0%) | 1/346 (0.3%) | ||
| Wound Infection | 0/354 (0%) | 1/346 (0.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Chest Injury | 0/354 (0%) | 1/346 (0.3%) | ||
| Femoral Neck Fracture | 1/354 (0.3%) | 0/346 (0%) | ||
| Femur Fracture | 2/354 (0.6%) | 4/346 (1.2%) | ||
| Foot Fracture | 0/354 (0%) | 1/346 (0.3%) | ||
| Humerus Fracture | 2/354 (0.6%) | 0/346 (0%) | ||
| Infusion Related Reaction | 0/354 (0%) | 1/346 (0.3%) | ||
| Skeletal Injury | 1/354 (0.3%) | 0/346 (0%) | ||
| Spinal Compression Fracture | 1/354 (0.3%) | 4/346 (1.2%) | ||
| Subarachnoid Haemorrhage | 0/354 (0%) | 1/346 (0.3%) | ||
| Toxicity to Various Agents | 0/354 (0%) | 1/346 (0.3%) | ||
| Traumatic Shock | 1/354 (0.3%) | 0/346 (0%) | ||
| Upper Limb Fracture | 0/354 (0%) | 1/346 (0.3%) | ||
| Wrist Fracture | 1/354 (0.3%) | 0/346 (0%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 1/354 (0.3%) | 0/346 (0%) | ||
| Aspartate Aminotransferase Increased | 2/354 (0.6%) | 0/346 (0%) | ||
| Blood Creatinine Increased | 1/354 (0.3%) | 1/346 (0.3%) | ||
| C-Reactive Protein Increased | 0/354 (0%) | 1/346 (0.3%) | ||
| Oxygen Saturation Decreased | 0/354 (0%) | 2/346 (0.6%) | ||
| Troponin Increased | 1/354 (0.3%) | 0/346 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 0/354 (0%) | 1/346 (0.3%) | ||
| Dehydration | 1/354 (0.3%) | 2/346 (0.6%) | ||
| Hyperkalaemia | 1/354 (0.3%) | 0/346 (0%) | ||
| Hypophagia | 0/354 (0%) | 1/346 (0.3%) | ||
| Tumour Lysis Syndrome | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/354 (0%) | 1/346 (0.3%) | ||
| Back Pain | 3/354 (0.8%) | 6/346 (1.7%) | ||
| Bone Pain | 1/354 (0.3%) | 2/346 (0.6%) | ||
| Dactylitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Neck Pain | 0/354 (0%) | 1/346 (0.3%) | ||
| Osteonecrosis | 1/354 (0.3%) | 0/346 (0%) | ||
| Spinal Column Stenosis | 0/354 (0%) | 1/346 (0.3%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute Myeloid Leukaemia | 1/354 (0.3%) | 0/346 (0%) | ||
| Adenocarcinoma of Colon | 1/354 (0.3%) | 0/346 (0%) | ||
| Bile Duct Cancer | 0/354 (0%) | 1/346 (0.3%) | ||
| Breast Cancer | 1/354 (0.3%) | 0/346 (0%) | ||
| Meningioma | 1/354 (0.3%) | 0/346 (0%) | ||
| Oesophageal Adenocarcinoma | 0/354 (0%) | 1/346 (0.3%) | ||
| Plasmacytoma | 0/354 (0%) | 1/346 (0.3%) | ||
| Rectal Adenocarcinoma | 1/354 (0.3%) | 0/346 (0%) | ||
| Renal Cell Carcinoma | 0/354 (0%) | 1/346 (0.3%) | ||
| Nervous system disorders | ||||
| Autonomic Nervous System Imbalance | 1/354 (0.3%) | 0/346 (0%) | ||
| Cerebral Infarction | 1/354 (0.3%) | 0/346 (0%) | ||
| Cerebral Ischaemia | 1/354 (0.3%) | 0/346 (0%) | ||
| Cerebrovascular Accident | 0/354 (0%) | 1/346 (0.3%) | ||
| Dizziness | 1/354 (0.3%) | 0/346 (0%) | ||
| Epilepsy | 0/354 (0%) | 1/346 (0.3%) | ||
| Haemorrhage Intracranial | 0/354 (0%) | 1/346 (0.3%) | ||
| Headache | 2/354 (0.6%) | 0/346 (0%) | ||
| Ischaemic Stroke | 1/354 (0.3%) | 2/346 (0.6%) | ||
| Neuralgia | 0/354 (0%) | 1/346 (0.3%) | ||
| Neurotoxicity | 1/354 (0.3%) | 0/346 (0%) | ||
| Paraesthesia | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Paraparesis | 0/354 (0%) | 1/346 (0.3%) | ||
| Parkinson's Disease | 0/354 (0%) | 1/346 (0.3%) | ||
| Peripheral Motor Neuropathy | 0/354 (0%) | 1/346 (0.3%) | ||
| Peripheral Sensorimotor Neuropathy | 0/354 (0%) | 1/346 (0.3%) | ||
| Peripheral Sensory Neuropathy | 2/354 (0.6%) | 2/346 (0.6%) | ||
| Sciatica | 0/354 (0%) | 1/346 (0.3%) | ||
| Somnolence | 0/354 (0%) | 1/346 (0.3%) | ||
| Spinal Cord Compression | 0/354 (0%) | 1/346 (0.3%) | ||
| Syncope | 0/354 (0%) | 1/346 (0.3%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/354 (0%) | 1/346 (0.3%) | ||
| Delirium | 1/354 (0.3%) | 0/346 (0%) | ||
| Depression | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Psychotic Disorder | 1/354 (0.3%) | 0/346 (0%) | ||
| Renal and urinary disorders | ||||
| Acute Kidney Injury | 5/354 (1.4%) | 3/346 (0.9%) | ||
| Anuria | 1/354 (0.3%) | 0/346 (0%) | ||
| Chronic Kidney Disease | 1/354 (0.3%) | 0/346 (0%) | ||
| Haematuria | 0/354 (0%) | 1/346 (0.3%) | ||
| Prerenal Failure | 1/354 (0.3%) | 0/346 (0%) | ||
| Renal Failure | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Urinary Retention | 1/354 (0.3%) | 0/346 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Distress Syndrome | 0/354 (0%) | 1/346 (0.3%) | ||
| Acute Respiratory Failure | 0/354 (0%) | 2/346 (0.6%) | ||
| Bronchiectasis | 0/354 (0%) | 1/346 (0.3%) | ||
| Bronchospasm | 0/354 (0%) | 2/346 (0.6%) | ||
| Chronic Obstructive Pulmonary Disease | 0/354 (0%) | 1/346 (0.3%) | ||
| Cough | 0/354 (0%) | 1/346 (0.3%) | ||
| Dyspnoea | 4/354 (1.1%) | 6/346 (1.7%) | ||
| Haemoptysis | 1/354 (0.3%) | 0/346 (0%) | ||
| Hypoxia | 0/354 (0%) | 2/346 (0.6%) | ||
| Interstitial Lung Disease | 0/354 (0%) | 1/346 (0.3%) | ||
| Laryngeal Oedema | 1/354 (0.3%) | 0/346 (0%) | ||
| Obstructive Airways Disorder | 1/354 (0.3%) | 0/346 (0%) | ||
| Pneumonitis | 0/354 (0%) | 1/346 (0.3%) | ||
| Pneumothorax Spontaneous | 1/354 (0.3%) | 0/346 (0%) | ||
| Pulmonary Embolism | 4/354 (1.1%) | 0/346 (0%) | ||
| Pulmonary Oedema | 0/354 (0%) | 6/346 (1.7%) | ||
| Tachypnoea | 0/354 (0%) | 1/346 (0.3%) | ||
| Wheezing | 0/354 (0%) | 1/346 (0.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Decubitus Ulcer | 0/354 (0%) | 1/346 (0.3%) | ||
| Erythema Multiforme | 2/354 (0.6%) | 0/346 (0%) | ||
| Rash Erythematous | 0/354 (0%) | 1/346 (0.3%) | ||
| Rash Vesicular | 1/354 (0.3%) | 0/346 (0%) | ||
| Vascular disorders | ||||
| Hypertension | 1/354 (0.3%) | 2/346 (0.6%) | ||
| Hypotension | 1/354 (0.3%) | 1/346 (0.3%) | ||
| Hypovolaemic Shock | 0/354 (0%) | 1/346 (0.3%) | ||
| Orthostatic Hypotension | 0/354 (0%) | 1/346 (0.3%) | ||
| Thrombophlebitis | 2/354 (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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 331/354 (93.5%) | 324/346 (93.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 131/354 (37%) | 94/346 (27.2%) | ||
| Leukopenia | 53/354 (15%) | 46/346 (13.3%) | ||
| Lymphopenia | 36/354 (10.2%) | 37/346 (10.7%) | ||
| Neutropenia | 186/354 (52.5%) | 171/346 (49.4%) | ||
| Thrombocytopenia | 189/354 (53.4%) | 168/346 (48.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 25/354 (7.1%) | 18/346 (5.2%) | ||
| Constipation | 64/354 (18.1%) | 63/346 (18.2%) | ||
| Diarrhoea | 87/354 (24.6%) | 81/346 (23.4%) | ||
| Dyspepsia | 12/354 (3.4%) | 18/346 (5.2%) | ||
| Nausea | 76/354 (21.5%) | 72/346 (20.8%) | ||
| Vomiting | 52/354 (14.7%) | 59/346 (17.1%) | ||
| General disorders | ||||
| Asthenia | 42/354 (11.9%) | 40/346 (11.6%) | ||
| Chills | 6/354 (1.7%) | 26/346 (7.5%) | ||
| Fatigue | 50/354 (14.1%) | 47/346 (13.6%) | ||
| Injection Site Erythema | 28/354 (7.9%) | 12/346 (3.5%) | ||
| Oedema Peripheral | 39/354 (11%) | 62/346 (17.9%) | ||
| Pyrexia | 70/354 (19.8%) | 78/346 (22.5%) | ||
| Infections and infestations | ||||
| Bronchitis | 25/354 (7.1%) | 44/346 (12.7%) | ||
| Nasopharyngitis | 20/354 (5.6%) | 19/346 (5.5%) | ||
| Pneumonia | 7/354 (2%) | 25/346 (7.2%) | ||
| Upper Respiratory Tract Infection | 48/354 (13.6%) | 87/346 (25.1%) | ||
| Urinary Tract Infection | 12/354 (3.4%) | 26/346 (7.5%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 46/354 (13%) | 40/346 (11.6%) | ||
| Hyperglycaemia | 13/354 (3.7%) | 21/346 (6.1%) | ||
| Hypocalcaemia | 17/354 (4.8%) | 20/346 (5.8%) | ||
| Hypokalaemia | 17/354 (4.8%) | 19/346 (5.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 22/354 (6.2%) | 26/346 (7.5%) | ||
| Back Pain | 40/354 (11.3%) | 42/346 (12.1%) | ||
| Bone Pain | 8/354 (2.3%) | 19/346 (5.5%) | ||
| Pain in Extremity | 22/354 (6.2%) | 29/346 (8.4%) | ||
| Nervous system disorders | ||||
| Dizziness | 21/354 (5.9%) | 22/346 (6.4%) | ||
| Headache | 12/354 (3.4%) | 23/346 (6.6%) | ||
| Neuralgia | 16/354 (4.5%) | 24/346 (6.9%) | ||
| Paraesthesia | 19/354 (5.4%) | 15/346 (4.3%) | ||
| Peripheral Sensory Neuropathy | 121/354 (34.2%) | 98/346 (28.3%) | ||
| Psychiatric disorders | ||||
| Insomnia | 32/354 (9%) | 26/346 (7.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 27/354 (7.6%) | 51/346 (14.7%) | ||
| Dyspnoea | 14/354 (4%) | 39/346 (11.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 10/354 (2.8%) | 19/346 (5.5%) | ||
| Rash | 39/354 (11%) | 29/346 (8.4%) | ||
| Vascular disorders | ||||
| Hypertension | 10/354 (2.8%) | 33/346 (9.5%) | ||
| Hypotension | 23/354 (6.5%) | 30/346 (8.7%) | ||
Limitations/Caveats
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/Title | Executive Medical Director |
|---|---|
| Organization | Janssen Research and Development, LLC |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
- CR104761
- 54767414MMY3007
- 2014-002272-88