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CompletedNCT03652064Updated Jun 2, 2026Results posted

A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

A Phase 3 interventional study of Daratumumab and Bortezomib in Multiple Myeloma, sponsored by Janssen Research & Development, LLC. Completed at 114 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-02.

Sponsored by Janssen Research & Development, LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
395
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.

Read the detailed description

This study will evaluate participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. The data available from other available studies suggests that addition of daratumumab with Velcade (bortezomib), lenalidomide, and dexamethasone [VRd] is anticipated to improve the response rates and the depth of response and may lead to improved long-term outcomes in newly diagnosed participants with MM. Daratumumab targets CD38, a protein expressed on the surface of MM cells and other hematopoietic cells. Bortezomib is a proteasome inhibitor, which plays a critical role in the pathogenesis of MM. Lenalidomide has cytotoxic effects on myeloma cells and is capable of inducing apoptosis, or programmed cell death and dexamethasone induces apoptosis in MM cells. The rationale for the study is to utilize the subcutaneous (SC) formulation of daratumumab instead of the intravenous (IV) formulation, which is expected to provide similar exposure and is expected to limit additional toxicity to participants, treated with this quadruplet regimen. The study will consist of 3 phases: Screening (up to 28 days before randomization), Treatment phase (from Cycle 1 [21 days] Day 1 and continues until disease progression) and Follow up (Postintervention). Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. Participants will undergo procedures like electrocardiogram (ECG), chest x-rays or full dose chest CT scans, Pulmonary function test (PFT), spirometry etc. during the course of study. Participants will also be monitored closely for adverse events (AEs), laboratory abnormalities, and clinical response. The duration of the study will be approximately 6.5 years.

02

Conditions studied

  • Multiple Myeloma

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03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 395 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Janssen Research & Development, LLC is the lead sponsor of 912 studies on the registry; 76 are open to participants now.

Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

- Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria Monoclonal plasma cells in the bone marrow greater than or equal to (>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria. CRAB criteria: Hypercalcemia: serum calcium greater than (>) 0.25 millimoles per liter (mmol/L) (>1 milligram per deciliter [mg/dL]) higher than upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL); Renal insufficiency: creatinine clearance less than (\<) 40 milliliter per minute (mL/min) or serum creatinine >177 micro millimoles per liter (umol/L) (>2 mg/dL); Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.

Biomarkers of Malignancy: Clonal bone marrow plasma cell percentage >=60%; Involved: uninvolved serum free light chain (FLC) ratio >=100; >1 focal lesion on magnetic resonance imaging (MRI) studies

  • Must have measurable disease, as assessed by central laboratory
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing
  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen

Exclusion criteria

Exclusion Criteria:

  • Frailty index of >=2 according to Myeloma Geriatric Assessment score
  • Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg dexamethasone or equivalent)
  • Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion 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)
  • 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 5
  • Focal radiation therapy within 14 days of randomization with the exception of palliative radiotherapy for symptomatic pain management. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
395 participants (actual)

Study arms

  • Active comparator
    Bortezomib + Lenalidomide + Dexamethasone (VRd) and Rd

    Participants will receive bortezomib 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 (cycle of 28 days); dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond (each cycle is of 28 days) followed by lenalidomide-dexamethasone (Rd) until disease progression or unacceptable toxicity. Participants aged greater than (\>)75 years or body mass index (BMI) less than (\<) 18.5 kilograms per meters (kg/m\^2) will receive dexamethasone 20 mg oral tablets on Days 1, 4, 8, and 11 of each cycle.

    Drug: Bortezomib · Drug: Lenalidomide · Drug: Dexamethasone

  • Experimental
    Daratumumab + VRd (D-VRd) and DRd

    Participants will receive daratumumab 1800 mg as SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3 through 8 and every 4 weeks for Cycle 9 and beyond; bortezomib 1.3 mg/m\^2 as SC injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9; dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond followed by daratumumab-lenalidomide-dexamethasone (DRd) until disease progression or unacceptable toxicity. Participants aged \>75 years or BMI \<18.5 kg/m\^2 will receive Dexamethasone 20 mg oral tablets on Days 1, 4, 8, and 11 of each cycle.

    Drug: Daratumumab · Drug: Bortezomib · Drug: Lenalidomide · Drug: Dexamethasone

Interventions

  • DrugDaratumumab

    Daratumumab (1800 mg) will be administered by SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3-8. For Cycle 9 and beyond, participants will receive daratumumab 1800 mg SC once every 4 weeks until documented disease progression or unacceptable toxicity.

    Also known as: JNJ-54767414, DARZALEX

  • DrugBortezomib

    Bortezomib 1.3 mg/m\^2 will be administered by SC injection twice weekly on Days 1, 4, 8, and 11 of each 21-day cycle for Cycles 1-8.

    Also known as: Velcade

  • DrugLenalidomide

    Lenalidomide will be self-administered at a dose of 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 and beyond until disease progression or unacceptable toxicity whichever occurs first.

    Also known as: Revlimid

  • DrugDexamethasone

    Dexamethasone will be self-administered orally, 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12 of each 21-day cycle for Cycles 1-8. During Cycle 9 and beyond dexamethasone, will be self-administered orally at a total dose of 40 mg on Days 1, 8, 15, 22 of each 28-day cycle.

06

What researchers measure

Primary outcomes

  1. Primary Analysis: Overall Minimal Residual Disease (MRD) Negative Rate

    Overall MRD negativity rate was defined as the percentage of participants who achieved complete response (CR) or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to progressive disease (PD), subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or stringent complete response (sCR) prior to subsequent anti-myeloma therapy in accordance with the International Myeloma Working Group (IMWG) criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) plasma cells (PCs) in bone marrow. sCR was defined as 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 (Day 1) up to 27.9 months

  2. Final Progression-Free Survival (PFS) Analysis : Overall Minimal Residual Disease (MRD) Negative Rate

    Overall MRD negativity rate was defined as the percentage of participants who achieved CR or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to PD, subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or sCR prior to subsequent anti-myeloma therapy in accordance with the IMWG criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5 % PCs in bone marrow. sCR was defined as CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

    Time frame: From randomization (Day 1) up to 64.8 months

Secondary outcomes

  1. Complete Response (CR) or Better Rate

    Time frame: From randomization (Day 1) up to 64.8 months

  2. Progression-Free Survival (PFS)

    Time frame: From randomization (Day 1) up to 64.8 months

  3. MRD Negativity Rate at 1 Year

    Time frame: At 1 Year

  4. Overall Response Rate (ORR)

    Time frame: From randomization (Day 1) up to 64.8 months

  5. Durable MRD Negative Rate

    Time frame: From randomization (Day 1) up to 64.8 months

  6. Very Good Partial Response (VGPR) or Better Rate

    Time frame: From randomization (Day 1) up to 64.8 months

  7. Duration of Response (DOR)

    Time frame: From randomization (Day 1) up to 64.8 months

  8. Time to Response

    Time frame: From randomization (Day 1) up to 64.8 months

  9. PFS on the Next Line of Therapy

    Time frame: From randomization (Day 1) up to 64.8 months

  10. Overall Survival (OS)

    Time frame: From screening (-28 Days) up to 64.8 months

  11. Overall MRD Negativity Rate in High-risk Molecular Subgroups

    Time frame: From randomization (Day 1) up to 64.8 months

  12. PFS in High-risk Molecular Subgroups

    Time frame: From randomization (Day 1) up to 64.8 months

  13. Maximum Observed Serum Concentration (Cmax) of Daratumumab

    Time frame: Predose on Day 1 and post dose on Day 4 of Cycles 1, 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8

  14. Minimum Observed Serum Concentration (Cmin) of Daratumumab

    Time frame: Predose on Day 1 and post dose on Day 4 of Cycles 1 and 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8

  15. Number of Participants With Anti-daratumumab Antibodies

    Time frame: Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8

  16. Number of Participants With Anti-recombinant Human Hyaluronidase PH20 (Anti-rHuPH20) Antibodies

    Time frame: Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8

  17. Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Item (EORTC QLQ-C30)

    Time frame: From screening (-28 Days) up to 64.8 months

  18. Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma 20-item (EORTC QLQ-MY20)

    Time frame: From screening (-28 Days) up to 64.8 months

  19. Mean Change From Baseline in EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)

    Time frame: From screening (-28 Days) up to 64.8 months

07

Results

Posted Apr 8, 2026

Participant flow

Participant flow — Overall Study
MilestoneArm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)
Started198197
Treated195197
Completed00
Not completed198197
Withdrew: Death5450
Withdrew: Withdrawal by subject1311
Withdrew: Lost to follow-up21
Withdrew: Randomized but not treated30
Withdrew: Ongoing126135

Outcome measures

PrimaryPrimary Analysis: Overall Minimal Residual Disease (MRD) Negative Rate

Overall MRD negativity rate was defined as the percentage of participants who achieved complete response (CR) or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to progressive disease (PD), subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or stringent complete response (sCR) prior to subsequent anti-myeloma therapy in accordance with the International Myeloma Working Group (IMWG) criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) plasma cells (PCs) in bone marrow. sCR was defined as 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 (Day 1) up to 27.9 months
Reported as:
Number · Percentage of participants
Primary Analysis: Overall Minimal Residual Disease (MRD) Negative Rate
Percentage of participantsArm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)
Primary Analysis: Overall Minimal Residual Disease (MRD) Negative Rate35.4 (28.7 to 42.4)53.3 (46.1 to 60.4)
Statistical analysis
  • Arm A: Bortezomib-lenalidomide-dexamethasone (VRd) vs Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd) · Fisher Exact · p = =0.0004 · Odds ratio (or): 2.07 · 95% CI 1.38 to 3.10
PrimaryFinal Progression-Free Survival (PFS) Analysis : Overall Minimal Residual Disease (MRD) Negative Rate

Overall MRD negativity rate was defined as the percentage of participants who achieved CR or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to PD, subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or sCR prior to subsequent anti-myeloma therapy in accordance with the IMWG criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5 % PCs in bone marrow. sCR was defined as CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

Time frame:
From randomization (Day 1) up to 64.8 months
Reported as:
Number · Percentage of participants
Final Progression-Free Survival (PFS) Analysis : Overall Minimal Residual Disease (MRD) Negative Rate
Percentage of participantsArm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)
Final Progression-Free Survival (PFS) Analysis : Overall Minimal Residual Disease (MRD) Negative Rate39.4 (32.5 to 46.6)60.9 (53.7 to 67.8)
Statistical analysis
  • Arm A: Bortezomib-lenalidomide-dexamethasone (VRd) vs Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd) · Fisher Exact · p = <0.0001 · Odds ratio (or): 2.37 · 95% CI 1.58 to 3.55
SecondaryComplete Response (CR) or Better Rate
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryProgression-Free Survival (PFS)
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryMRD Negativity Rate at 1 Year
Time frame:
At 1 Year

Results for this outcome have not been posted.

SecondaryOverall Response Rate (ORR)
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryDurable MRD Negative Rate
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryVery Good Partial Response (VGPR) or Better Rate
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryDuration of Response (DOR)
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryTime to Response
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryPFS on the Next Line of Therapy
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryOverall Survival (OS)
Time frame:
From screening (-28 Days) up to 64.8 months

Results for this outcome have not been posted.

SecondaryOverall MRD Negativity Rate in High-risk Molecular Subgroups
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryPFS in High-risk Molecular Subgroups
Time frame:
From randomization (Day 1) up to 64.8 months

Results for this outcome have not been posted.

SecondaryMaximum Observed Serum Concentration (Cmax) of Daratumumab
Time frame:
Predose on Day 1 and post dose on Day 4 of Cycles 1, 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8

Results for this outcome have not been posted.

SecondaryMinimum Observed Serum Concentration (Cmin) of Daratumumab
Time frame:
Predose on Day 1 and post dose on Day 4 of Cycles 1 and 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8

Results for this outcome have not been posted.

SecondaryNumber of Participants With Anti-daratumumab Antibodies
Time frame:
Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8

Results for this outcome have not been posted.

SecondaryNumber of Participants With Anti-recombinant Human Hyaluronidase PH20 (Anti-rHuPH20) Antibodies
Time frame:
Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8

Results for this outcome have not been posted.

SecondaryMean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Item (EORTC QLQ-C30)
Time frame:
From screening (-28 Days) up to 64.8 months

Results for this outcome have not been posted.

SecondaryMean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma 20-item (EORTC QLQ-MY20)
Time frame:
From screening (-28 Days) up to 64.8 months

Results for this outcome have not been posted.

SecondaryMean Change From Baseline in EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)
Time frame:
From screening (-28 Days) up to 64.8 months

Results for this outcome have not been posted.

Adverse events

Collected over Serious adverse events (SAE) and other adverse events (AEs): From start of treatment (Day 1) up to 30 days after the last dose of study treatment (up to 64.8 months); All-cause mortality: From screening (Day -28) up to 64.8 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm A: Bortezomib-lenalidomide-dexamethasone (VRd)59/198 (29.8%)131/195 (67.2%)191/195 (97.9%)
Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)51/197 (25.9%)142/197 (72.1%)196/197 (99.5%)
Most frequent serious events
Showing 10 of 279
Most frequent serious events
EventArm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)
PneumoniaInfections and infestations25/19527/197
Covid-19Infections and infestations16/19522/197
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders5/19511/197
DiarrhoeaGastrointestinal disorders6/19510/197
Covid-19 PneumoniaInfections and infestations4/1958/197
Atrial FibrillationCardiac disorders7/1957/197
SepsisInfections and infestations4/1957/197
Urinary Tract InfectionInfections and infestations4/1957/197
SyncopeNervous system disorders6/1953/197
AnaemiaBlood and lymphatic system disorders2/1956/197
Most frequent other events
Showing 10 of 109
Most frequent other events
EventArm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)
Peripheral Sensory NeuropathyNervous system disorders118/195110/197
DiarrhoeaGastrointestinal disorders112/195111/197
NeutropeniaBlood and lymphatic system disorders76/195108/197
ThrombocytopeniaBlood and lymphatic system disorders66/19591/197
Oedema PeripheralGeneral disorders76/19583/197
ConstipationGastrointestinal disorders82/19575/197
Upper Respiratory Tract InfectionInfections and infestations64/19577/197
AnaemiaBlood and lymphatic system disorders62/19571/197
InsomniaPsychiatric disorders63/19563/197
FatigueGeneral disorders60/19563/197

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)Total
Median70.0 (31 to 80)70.0 (42 to 79)70 (31 to 80)
Sex: Female, Male
Sex: Female, Male(Participants)Arm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)Total
Female87110197
Male11187198
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)Total
Hispanic or Latino353166
Not Hispanic or Latino147154301
Unknown or Not Reported161228
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Arm A: Bortezomib-lenalidomide-dexamethasone (VRd)Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd)Total
White156162318
Black or African American91019
Asian141125
Native Hawaiian or other Pacific Islander101
Other213
Not reported161329
08

Study locations

114 sites
  • Innovative Clinical Research Inc
    Cerritos, California 90703, United States
  • Baptist MD Anderson
    Jacksonville, Florida 32207, United States
  • Fort Wayne Medical Oncology and Hematology, Inc.
    Fort Wayne, Indiana 46804, United States
  • Norton Healthcare
    Louisville, Kentucky 40207, United States
  • Tufts Medical Center
    Boston, Massachusetts 02111, United States
  • Boston University Medical Center
    Boston, Massachusetts 02118, United States
  • Cancer And Hematology Centers of Western Michigan PC
    Grand Rapids, Michigan 49503, United States
  • Saint Lukes Hospital Saint Lukes Cancer Specialists
    Kansas City, Missouri 64111, United States
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey 08901, United States
  • San Juan Oncology Associates
    Farmington, New Mexico 87401, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • NYU Winthrop
    Mineola, New York 11501, United States
  • Levine Cancer Institute
    Charlotte, North Carolina 28204, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Good Samaritan Hospital Corvallis
    Corvallis, Oregon 97330, United States
  • University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
    Pittsburgh, Pennsylvania 15232 1301, United States
  • Gibbs Cancer Center
    Spartanburg, South Carolina 29303, United States
  • University of Texas, MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • University of Virginia
    Charlottesville, Virginia 22908, United States
  • Universidade Estadual De Campinas
    Campinas, 13083-878, Brazil
  • Liga Norte Riograndense Contra O Cancer
    Natal, 59062 000, Brazil
  • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
    Porto Alegre, 90610-000, Brazil
  • Ministerio da Saude Instituto Nacional do Cancer
    Rio de Janeiro, 20230-130, Brazil
  • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
    Rio de Janeiro, 22775 001, Brazil
  • Instituto de Ensino e Pesquisa São Lucas
    São Paulo, 01227-200, Brazil
  • Real e Benemerita Associacao Portuguesa de Beneficencia
    São Paulo, 01323 900, Brazil
  • Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
    São Paulo, 03102-002, Brazil
  • Hospital Santa Cruz
    São Paulo, 04122-000, Brazil
  • Clinica Medica Sao Germano S/S LTDA
    São Paulo, 04537-081, Brazil
  • Arthur J E Child Comprehensive Cancer Centre
    Calgary, Alberta T2N 5G2, Canada
  • Cross Cancer Institute
    Edmonton, Alberta T6G 1Z2, Canada
  • The Gordon & Leslie Diamond Health Care Center
    Vancouver, British Columbia V5Z 1M9, Canada
  • QEII Health Sciences Centre
    Halifax, Nova Scotia B3H 1V7, Canada
  • Brampton Civic Hospital
    Brampton, Ontario L6R 3J7, Canada
  • Victoria Hospital
    London, Ontario N6A 5W9, Canada
  • Lakeridge Health Oshawa
    Oshawa, Ontario L1G-2B9, Canada
  • McGill University Health Centre
    Montreal, Quebec H4A 3J1, Canada
  • CHU de Quebec L Hotel Dieu de Quebec
    Québec, Quebec G1J 1Z4, Canada
  • Fakultni nemocnice Brno
    Brno, 625 00, Czechia
  • Fakultni nemocnice Hradec Kralove
    Hradec Králové, 500 05, Czechia
  • Fakultni Nemocnice Ostrava
    Ostrava, 708 52, Czechia
  • Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
    Pilsen, 323 00, Czechia
  • Vseobecna fakultni nemocnice v Praze
    Prague, 128 08, Czechia
  • CHU Henri Mondor
    Créteil, 94010, France
  • Centre Hospitalier Départmental La Roche sur Yon
    La Roche-sur-Yon, 85925, France
  • Hopital Claude Huriez
    Lille, 59037, France
  • Institut Paoli Calmettes
    Marseille, 13009, France
  • CHU de Montpellier Hopital Saint Eloi
    Montpellier, 34295, France
  • CHU de Bordeaux - Hospital Haut-Leveque
    Pessac, 33604, France
  • Strasbourg Oncologie Libérale
    Strasbourg, 67000, France
  • Institut Universitaire du cancer de Toulouse-Oncopole
    Toulouse, 31059, France
  • phase 3 - Hämatoonkologischer Studienkreis am Klinikum Aschaffenburg
    Aschaffenburg, 63739, Germany
  • Universitatsklinikum Freiburg
    Freiburg im Breisgau, 79106, Germany
  • St. Josef-Krankenhaus Hamm-Bockum-Hövel
    Hamm, 59075, Germany
  • Institut für Versorgungsforschung
    Koblenz, 56068, Germany
  • Universitatsmedizin Leipzig
    Leipzig, 4103, Germany
  • Klinikum Großhadern der Ludwig-Maximilians-Universität
    München, 81377, Germany
  • Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
    Tübingen, 72076, Germany
  • Barzilai Medical Center
    Ashkelon, 78741, Israel
  • Hillel Yaffe Medical Center
    Hadera, 38100, Israel
  • Rambam Med.Center - Hematology Institute
    Haifa, 3109601, Israel
  • Carmel Medical Center
    Haifa, 3436212, Israel
  • Meir Hospital
    Kfar Saba, 44281, Israel
  • Rabin Medical Center
    Petah Tikva, 49100, Israel
  • Sheba Medical Center
    Ramat Gan, 52621, Israel
  • Sourasky (Ichilov) Medical Center
    Tel Aviv, 64239, Israel
  • Fukuoka University Hospital
    Fukuoka, 814-0180, Japan
  • Ogaki Municipal Hospital
    Gifu, 503-8502, Japan
  • Kanazawa University Hospital
    Kanazawa, 920 8641, Japan
  • Kobe City Medical Center General Hospital
    Kobe, 650 0047, Japan
  • National Hospital Organization Kumamoto Medical Center
    Kumamoto, 860-0008, Japan
  • University Hospital Kyoto Prefectural University of Medicine
    Kyoto, 602-8566, Japan
  • National Hospital Organization Matsumoto Medical Center
    Matsumoto, 399-8701, Japan
  • Matsuyama Red Cross Hospital
    Matsuyama, 790-8524, Japan
  • Nagoya City University Hospital
    Nagoya, 467 8602, Japan
  • National Hospital Organization Okayama Medical Center
    Okayama, 701-1192, Japan
  • Japanese Red Cross Osaka Hospital
    Osaka, 543 8555, Japan
  • National Hospital Organization Shibukawa Medical Center
    Shibukawa, 377-0280, Japan
  • Japanese Red Cross Medical Center
    Shibuya City, 150-8935, Japan
  • VU Medisch Centrum
    Amsterdam, 1081 HV, Netherlands
  • Albert Schweitzer ziekenhuis-lokatie Dordwijk
    Dordrecht, 3318 AT, Netherlands
  • Erasmus MC
    Rotterdam, 3015CE, Netherlands
  • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
    Brzozów, 36-200, Poland
  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
    Chorzów, 41-500, Poland
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, 80 214, Poland
  • Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
    Kielce, 25 734, Poland
  • NSSU Szpital Uniwersytecki w Krakowie
    Krakow, 30 688, Poland
  • Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli
    Lublin, 20090, Poland
  • Uniwersytecki Szpital Kliniczny w Poznaniu
    Poznan, 60-569, Poland
  • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
    Słupsk, 76-200, Poland
  • Instytut Hematologii i Transfuzjologii
    Warsaw, 02 776, Poland
  • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
    Warsaw, 02-781, Poland
  • Hosp. Univ. Fundacion Alcorcon
    Alcorcón, 28922, Spain
  • Hosp. Del Mar
    Barcelona, 08003, Spain
  • Hosp. Univ. de Guadalajara
    Guadalajara, 19002, Spain
  • Hosp. Univ. Pta. de Hierro Majadahonda
    Majadahonda, 28222, Spain
  • Hosp. Quiron Madrid Pozuelo
    Pozuelo de Alarcón, 28223, Spain
  • Hosp. Mutua Terrassa
    Terrassa, 08221, Spain
  • Gulhane Egitim ve Arastirma Hastanesi
    Ankara, 06010, Turkey (Türkiye)
  • Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
    Ankara, 06200, Turkey (Türkiye)

Showing the first 100 of 114 sites across 13 countries.

09

References and documents

Publications

  • Zweegman S, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, Pour L, Marti J, Basu S, Cohen YC, Matsumoto M, Suzuki K, Hulin C, Legiec WM, Beksac M, Maiolino A, Takamatsu H, Perrot A, Turgut M, Liu W, Wang J, Van Brummelen E, Krevvata M, Lopez-Masi L, Carey J, Borgsten F, Rowe M, Carson R, Usmani SZ. Daratumumab in Transplant-Ineligible or -Deferred Newly Diagnosed Multiple Myeloma: Minimal Residual Disease in CEPHEUS. Blood Adv. 2026 Jun 3:bloodadvances.2026019937. doi: 10.1182/bloodadvances.2026019937. Online ahead of print. PubMed 42234958 ↗
  • Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, Pour L, Marti JM, Basu S, Cohen YC, Matsumoto M, Suzuki K, Hulin C, Grosicki S, Legiec W, Beksac M, Maiolino A, Takamatsu H, Perrot A, Turgut M, Ahmadi T, Liu W, Wang J, Chastain K, Vermeulen J, Krevvata M, Lopez-Masi L, Carey J, Rowe M, Carson R, Zweegman S. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025 Apr;31(4):1195-1202. doi: 10.1038/s41591-024-03485-7. Epub 2025 Feb 5. PubMed 39910273 ↗
  • Abdallah N, Kumar SK. Up-Front Treatment of Elderly (Age >/=75 Years) and Frail Patients With Multiple Myeloma. J Natl Compr Canc Netw. 2024 Nov;22(9):e247039. doi: 10.6004/jnccn.2024.7039. PubMed 39536451 ↗

Study documents

  • Study protocol · Mar 14, 2024
  • Statistical analysis plan · May 28, 2021

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 2, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03652064
Lead sponsor
Janssen Research & Development, LLC
Responsible party
Sponsor
First posted
Aug 29, 2018
Start date
Nov 6, 2018
Primary completion
May 7, 2024
Completion
Apr 21, 2026
Results posted
Apr 8, 2026
Last update
Jun 2, 2026

Study contacts

Janssen Research & Development, LLC Clinical Trial
study director · Janssen Research & Development, LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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