Last reviewed · How we verify

NCT02874742

Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma

Completed Phase 2 Results posted Last updated 4 February 2025
What this trial tests

Phase 2 trial testing Lenalidomide in Multiple Myeloma in 224 participants. Completed in 8 April 2022.

Timeline
29 August 2016
Primary endpoint
25 January 2019
8 April 2022

Quick facts

Lead sponsorJanssen Research & Development, LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment224
Start date29 August 2016
Primary completion25 January 2019
Estimated completion8 April 2022
Sites36 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 70, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Stringent Complete Response (sCR) Primary · From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)

Percentage of participants who had achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluor

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)32.022.9 – 42.2
Randomized: Daratumumab+RVd (D-RVd)42.432.5 – 52.8
Percentage of Participants With Complete Response (CR) or Better Secondary · From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)

CR or better rate is defined as the percentage of participants who achieve CR or sCR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5% PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. For 2 participants (1 in each randomized treatment group), data were updated by the study sites which resulted in their inclusion to the response-evaluable analysis set af

At the end of induction prior to ASCT
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)13.47.3 – 21.8
Randomized: Daratumumab+RVd (D-RVd)19.212.0 – 28.3
Safety Run-in: D-RVd12.51.6 – 38.3
At the end of ASCT prior to consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)19.612.2 – 28.9
Randomized: Daratumumab+RVd (D-RVd)27.318.8 – 37.1
Safety Run-in: D-RVd56.329.9 – 80.2
At the end of post-ASCT consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)42.332.3 – 52.7
Randomized: Daratumumab+RVd (D-RVd)51.541.3 – 61.7
Safety Run-in: D-RVd68.841.3 – 89.0
At the end of maintenance period (up to 24 Months)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)60.249.8 – 70.0
Randomized: Daratumumab+RVd (D-RVd)83.074.2 – 89.8
Safety Run-in: D-RVd93.869.8 – 99.8
Percentage of Participants With Overall Stringent Complete Response (sCR) Secondary · From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)

Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

At the end of induction prior to ASCT
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)7.23.0 – 14.3
Randomized: Daratumumab+RVd (D-RVd)12.16.4 – 20.2
Safety Run-in: D-RVd0NA – NA
At the end of ASCT prior to consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)14.48.1 – 23.0
Randomized: Daratumumab+RVd (D-RVd)21.213.6 – 30.6
Safety Run-in: D-RVd43.819.8 – 70.1
At the end of post-ASCT consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)32.022.9 – 42.2
Randomized: Daratumumab+RVd (D-RVd)42.432.5 – 52.8
Safety Run-in: D-RVd56.329.9 – 80.2
At the end of Maintenance Treatment (up to 24 Months)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)48.037.8 – 58.3
Randomized: Daratumumab+RVd (D-RVd)67.056.9 – 76.1
Safety Run-in: D-RVd93.869.8 – 99.8
Percentage of Participants With Overall Response Rate (ORR) Secondary · From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)

ORR- percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response \[VGPR\], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (\>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required. A \>=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by

At the end of induction prior to ASCT
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)91.884.4 – 96.4
Randomized: Daratumumab+RVd (D-RVd)98.092.9 – 99.8
Safety Run-in: D-RVd10079.4 – 100
At the end of ASCT prior to consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)91.884.4 – 96.4
Randomized: Daratumumab+RVd (D-RVd)99.094.5 – 100
Safety Run-in: D-RVd10079.4 – 100
At the end of post-ASCT consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)91.884.4 – 96.4
Randomized: Daratumumab+RVd (D-RVd)99.094.5 – 100
Safety Run-in: D-RVd10079.4 – 100
At the End of Maintenance Treatment (up to 24 Months)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)91.884.5 – 96.4
Randomized: Daratumumab+RVd (D-RVd)99.094.6 – 100.0
Safety Run-in: D-RVd100.079.4 – 100.0
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better Secondary · From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)

VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours.

At the end of induction prior to ASCT
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)56.746.3 – 66.7
Randomized: Daratumumab+RVd (D-RVd)71.761.8 – 80.3
Safety Run-in: D-RVd68.841.3 – 89.0
At the end of ASCT prior to consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)66.055.7 – 75.3
Randomized: Daratumumab+RVd (D-RVd)86.978.6 – 92.8
Safety Run-in: D-RVd10079.4 – 100
At the end of post-ASCT consolidation
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)73.263.2 – 81.7
Randomized: Daratumumab+RVd (D-RVd)90.983.4 – 95.8
Safety Run-in: D-RVd10079.4 – 100
At the End of Maintenance Period (up to 24 Months)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)77.668.0 – 85.4
Randomized: Daratumumab+RVd (D-RVd)96.090.1 – 98.9
Safety Run-in: D-RVd100.079.4 – 100.0
Percentage of Participants With Negative Minimal Residual Disease (MRD) Secondary · From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months), and at the end of maintenance period of 24 months (overall duration up to 34 months)

Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (\<) 10\^5.

MRD from randomization to prior to ASCT (10^5)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)7.83.4 – 14.7
Randomized: Daratumumab+RVd (D-RVd)22.114.6 – 31.3
Safety Run-in: D-RVd18.84.0 – 45.6
Post ASCT consolidation (10^5)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)20.413.1 – 29.5
Randomized: Daratumumab+RVd (D-RVd)50.040.0 – 60.0
Safety Run-in: D-RVd50.024.7 – 75.3
At the End of Maintenance Period (up to 24 Months) (10^5)
GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)30.121.5 – 39.9
Randomized: Daratumumab+RVd (D-RVd)64.454.4 – 73.6
Safety Run-in: D-RVd81.354.4 – 96.0
Duration of Complete Response or Better Secondary · From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)

Duration of CR or better is the duration from the date of initial documentation of a CR or sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to \[\>=\] 0.5 gram per deciliter \[g/dL\] and \>=200 milligrams \[mg\]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved an

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)NANA – NA
Randomized: Daratumumab+RVd (D-RVd)NANA – NA
Safety Run-in: D-RVdNANA – NA
Duration of Stringent Complete Response (sCR) Secondary · From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)

Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be \>= 0.5 g/dL and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be \> 10 mg/dL); Definite development

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)NANA – NA
Randomized: Daratumumab+RVd (D-RVd)NANA – NA
Safety Run-in: D-RVdNA42.4 – NA
Time to Stringent Complete Response (sCR) Secondary · From randomization to the date of initial documentation of sCR (up to 5 years)

Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria.

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)14.39.2 – 21.7
Randomized: Daratumumab+RVd (D-RVd)10.28.8 – 13.0
Safety Run-in: D-RVd8.47.1 – 15.2
Time to Complete Response or Better Secondary · From randomization to the date of initial documentation of CR (up to 5 years)

Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)9.68.4 – 12.2
Randomized: Daratumumab+RVd (D-RVd)8.97.9 – 9.4
Safety Run-in: D-RVd7.76.7 – 9.7
Time to Very Good Partial Response (VGPR) or Better Secondary · From randomization to the date of initial documentation of VGPR or better (up to 5 years)

Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)3.02.2 – 6.3
Randomized: Daratumumab+RVd (D-RVd)2.22.1 – 2.7
Safety Run-in: D-RVd2.10.9 – 6.7
Time to Partial Response (PR) or Better Secondary · From randomization to the date of initial documentation of PR or better (up to 5 years)

Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

GroupValue95% CI
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)0.80.8 – 1.0
Randomized: Daratumumab+RVd (D-RVd)0.80.8 – 0.8
Safety Run-in: D-RVd0.80.7 – 1.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Other adverse events and serious adverse events: up to 30 days after the last dose of study treatment (up to 3 years); All-cause mortality: up to end of study (up to 5 years). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)
Serious: 53/102 (52%)
Deaths: 7/103
Randomized: Daratumumab+RVd (D-RVd)
Serious: 46/99 (46%)
Deaths: 7/104
Safety Run-in: D-RVd
Serious: 12/16 (75%)
Deaths: 1/16

Serious adverse events (105 terms)

ReactionSystemRandomized: Lenalidomide+B…Randomized: Daratumumab+RV…Safety Run-in: D-RVd
PneumoniaInfections and infestations
PyrexiaGeneral disorders
InfluenzaInfections and infestations
DiarrhoeaGastrointestinal disorders
Acute Kidney InjuryRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
Abdominal PainGastrointestinal disorders
NauseaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Squamous Cell Carcinoma of SkinNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnaemiaBlood and lymphatic system disorders
Small Intestinal ObstructionGastrointestinal disorders
VomitingGastrointestinal disorders
Non-Cardiac Chest PainGeneral disorders
BronchitisInfections and infestations
SepsisInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Back PainMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
NeuralgiaNervous system disorders
Peripheral Sensory NeuropathyNervous system disorders
SyncopeNervous system disorders
Drug Reaction with Eosinophilia and Systemic SymptomsSkin and subcutaneous tissue disorders
Other adverse events (302 terms — click to expand)

ReactionSystemRandomized: Lenalidomide+B…Randomized: Daratumumab+RV…Safety Run-in: D-RVd
FatigueGeneral disorders
Upper Respiratory Tract InfectionInfections and infestations
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
InsomniaPsychiatric disorders
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Neuropathy PeripheralNervous system disorders
Back PainMusculoskeletal and connective tissue disorders
LeukopeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Peripheral Sensory NeuropathyNervous system disorders
AnaemiaBlood and lymphatic system disorders
Oedema PeripheralGeneral disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
LymphopeniaBlood and lymphatic system disorders
Muscle SpasmsMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypokalaemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
RashSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
Rash Maculo-PapularSkin and subcutaneous tissue disorders
Abdominal PainGastrointestinal disorders
Decreased AppetiteMetabolism and nutrition disorders
DysgeusiaNervous system disorders
ParaesthesiaNervous system disorders
HyperglycaemiaMetabolism and nutrition disorders
Pain in ExtremityMusculoskeletal and connective tissue disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
Vision BlurredEye disorders
Influenza Like IllnessGeneral disorders
Alanine Aminotransferase IncreasedInvestigations
Aspartate Aminotransferase IncreasedInvestigations
AnxietyPsychiatric disorders

Most-reported serious reactions: Pneumonia, Pyrexia, Influenza, Diarrhoea, Acute Kidney Injury, Dyspnoea, Pulmonary Embolism, Febrile Neutropenia.

Data from ClinicalTrials.gov NCT02874742 adverse events section.

Sponsor's own description

The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial.
    Voorhees PM, Kaufman JL, Laubach J, Sborov DW, et al · · 2020 · cited 510× · PMID 32325490 · DOI 10.1182/blood.2020005288
  2. Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma.
    Leypoldt LB, Tichy D, Besemer B, Hänel M, et al · · 2024 · cited 115× · PMID 37753960 · DOI 10.1200/jco.23.01696
  3. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial.
    Voorhees PM, Sborov DW, Laubach J, Kaufman JL, et al · · 2023 · cited 114× · PMID 37708911 · DOI 10.1016/s2352-3026(23)00217-x
  4. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma.
    Dimopoulos MA, Jakubowiak AJ, McCarthy PL, Orlowski RZ, et al · · 2020 · cited 87× · PMID 32054831 · DOI 10.1038/s41408-020-0273-x
  5. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma.
    Landgren O, Prior TJ, Masterson T, Heuck C, et al · · 2024 · cited 85× · PMID 38768337 · DOI 10.1182/blood.2024024371
  6. Emerging agents and regimens for multiple myeloma.
    Yang Y, Li Y, Gu H, Dong M, et al · · 2020 · cited 57× · PMID 33168044 · DOI 10.1186/s13045-020-00980-5
  7. Update on the role of lenalidomide in patients with multiple myeloma.
    Holstein SA, Suman VJ, McCarthy PL. · · 2018 · cited 39× · PMID 30013765 · DOI 10.1177/2040620718775629
  8. Evaluating Daratumumab in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy.
    Dima D, Dower J, Comenzo RL, Varga C. · · 2020 · cited 36× · PMID 32904669 · DOI 10.2147/cmar.s212526

Verify or expand the search:

Other trials of Lenalidomide

Trials testing the same drug.

Other recruiting trials for Multiple Myeloma

Currently open trials in the same condition.

Other Janssen Research & Development, LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02874742.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing