Multiple MyelomaPhase 2NCT02874742
Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma
A Phase 2 study testing Lenalidomide, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 36 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Lenalidomide, Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 36 sitesUnited States
- Study dates
- 29 Aug 2016to 8 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
- Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
- A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose
Who cannot join
- Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
- Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
- Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<)50 percent (%) of predicted normal
- Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
- Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study
Trial locations and contacts
36 sites in 1 country.
36 sites in 1 country
United States36 sites
Study site
Abington, Pennsylvania
Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Baltimore, Maryland
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Buffalo, New York
Study site
Chapel Hill, North Carolina
Study site
Charlotte, North Carolina
Study site
Chicago, Illinois
Study site
Columbus, Ohio
Study site
Dallas, Texas
Study site
Detroit, Michigan
Study site
Duarte, California
Study site
Durham, North Carolina
Study site
Houston, Texas
Study site
La Jolla, California
Study site
Los Angeles, California
Study site
Milwaukee, Wisconsin
Study site
Nashville, Tennessee
Study site
New Orleans, Louisiana
Study site
New York, New York
Study site
Omaha, Nebraska
Study site
Orlando, Florida
Study site
Philadelphia, Pennsylvania
Study site
Portland, Oregon
Study site
Salt Lake City, Utah
Study site
San Francisco, California
Study site
Seattle, Washington
Study site
Spokane, Washington
Study site
St Louis, Missouri
Study site
Tampa, Florida
Study site
Washington D.C., District of Columbia
Study site
Westwood, Kansas
Study site
Winston-Salem, North Carolina
Study site
Worcester, Massachusetts
About this study
Official title: Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy and Autologous Stem Cell Transplantation
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.
- Conditions
- Multiple Myeloma
- Being tested
- Lenalidomide, Bortezomib, Dexamethasone, Daratumumab
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.
BortezomibDrug
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.
DexamethasoneDrug
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).
DaratumumabDrug
Daratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd) | Experimental | Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab. Receives: Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab |
| Lenalidomide+Bortezomib+Dexamethasone (RVd) | Experimental | Participants will receive lenalidomide, bortezomib and dexamethasone. Receives: Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Stringent Complete Response (sCR)
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 immunofluorescence or 2 to 4-color flow cytometry.
Measured: From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)
Secondary outcomes (15)
Percentage of Participants With Complete Response (CR) or Better
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 after the primary analysis.
Measured: 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)
Percentage of Participants With Overall Stringent Complete Response (sCR)
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.
Measured: 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)
Percentage of Participants With Overall Response Rate (ORR)
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 immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
Measured: 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)
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
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.
Measured: 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)
Percentage of Participants With Negative Minimal Residual Disease (MRD)
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.
Measured: 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)
Duration of Complete Response or Better
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 and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to plasma cells (PCs) proliferative disorder.
Measured: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)
Duration of Stringent Complete Response (sCR)
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 of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Measured: From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)
Time to Stringent Complete Response (sCR)
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.
Measured: From randomization to the date of initial documentation of sCR (up to 5 years)
Time to Complete Response or Better
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.
Measured: From randomization to the date of initial documentation of CR (up to 5 years)
Time to Very Good Partial Response (VGPR) or Better
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.
Measured: From randomization to the date of initial documentation of VGPR or better (up to 5 years)
Time to Partial Response (PR) or Better
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.
Measured: From randomization to the date of initial documentation of PR or better (up to 5 years)
Progression-free Survival (PFS)
PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. 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 of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Measured: From randomization to the date of first documented evidence of progressive disease or death (up to 5 years)
Overall Survival (OS)
OS is measured from the date of randomization to the date of the participant's death.
Measured: From randomization to the date of initial documentation of participant's death (up to 5 years)
Time to Progression (TTP)
TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria.
Measured: From randomization to the date of first documented evidence of progressive disease (up to 5 years)
Duration of Response
Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. 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 of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Measured: From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2016 (estimated)
- Study start29 Aug 2016
- Primary completion25 Jan 2019
- Study completion8 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02874742
- Sponsor's protocol ID
- CR108195
- Other IDs
- 54767414MMY2004
- Status last verified
- Jan 2025
- First submitted
- 1 Aug 2016
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- No
Publications
Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma. Future Oncol. 2025 Jan;21(1):25-49. doi: 10.1080/14796694.2024.2408909. Epub 2024 Oct 25.
PubMed 39452950Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, van de Donk NWCJ, Katodritou E, Schjesvold F, Balari AS, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P. A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma. Future Oncol. 2024;20(38):3043-3063. doi: 10.1080/14796694.2024.2394323. Epub 2024 Sep 17.
PubMed 39287147Chari A, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024 Jul 8;14(1):107. doi: 10.1038/s41408-024-01088-6.
PubMed 38977707Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
PubMed 38649340Silbermann R, Laubach J, Kaufman JL, Sborov DW, Reeves B, Rodriguez C, Chari A, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Orlowski RZ, Shain KH, Cowan AJ, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Health-related quality of life in transplant-eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient-reported outcomes from GRIFFIN. Am J Hematol. 2024 Jul;99(7):1257-1268. doi: 10.1002/ajh.27326. Epub 2024 Apr 15.
PubMed 38622840Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. 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. Lancet Haematol. 2023 Oct;10(10):e825-e837. doi: 10.1016/S2352-3026(23)00217-X. Epub 2023 Sep 11.
PubMed 37708911Nooka AK, Kaufman JL, Rodriguez C, Jakubowiak A, Efebera Y, Reeves B, Wildes T, Holstein SA, Anderson LD Jr, Badros A, Shune L, Chari A, Pei H, Cortoos A, Patel S, Lin TS, Richardson PG, Voorhees P. A plain language summary of daratumumab plus lenalidomide/bortezomib/dexamethasone in transplant-eligible Black patients with newly diagnosed multiple myeloma in the GRIFFIN study. Future Oncol. 2022 Dec;18(40):4443-4456. doi: 10.2217/fon-2022-0775. Epub 2023 Feb 17.
PubMed 36799429Sborov DW, Baljevic M, Reeves B, Laubach J, Efebera YA, Rodriguez C, Costa LJ, Chari A, Silbermann R, Holstein SA, Anderson LD Jr, Kaufman JL, Shah N, Pei H, Patel S, Cortoos A, Bartlett JB, Vermeulen J, Lin TS, Voorhees PM, Richardson PG. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022 Nov;199(3):355-365. doi: 10.1111/bjh.18432. Epub 2022 Sep 16.
PubMed 36111391Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.
PubMed 35985959Voorhees PM, Rodriguez C, Reeves B, Nathwani N, Costa LJ, Lutska Y, Bobba P, Hoehn D, Pei H, Ukropec J, Qi M, Lin TS, Richardson PG. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.
PubMed 33606004Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Murphy S, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin TS, Richardson PG. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945. doi: 10.1182/blood.2020005288.
PubMed 32325490
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy and Autologous Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02874742
- Acronym / sponsor ID
- CR108195
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 29 Aug 2016 (actual)
- Primary completion
- 25 Jan 2019 (actual)
- Study completion
- 8 Apr 2022 (actual)
- First posted
- 22 Aug 2016 (estimated)
- Results
- Posted 7 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd) | Experimental | Drug: Lenalidomide, Drug: Bortezomib, Drug: Dexamethasone, Drug: DaratumumabParticipants will receive lenalidomide, bortezomib, dexamethasone and daratumumab. |
| Lenalidomide+Bortezomib+Dexamethasone (RVd) | Experimental | Drug: Lenalidomide, Drug: Bortezomib, Drug: DexamethasoneParticipants will receive lenalidomide, bortezomib and dexamethasone. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
- Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
- A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose
Key exclusion criteria (5 listed)
- Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
- Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
- Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<)50 percent (%) of predicted normal
- Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
- Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenalidomideCycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern. | Drug | Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd), Lenalidomide+Bortezomib+Dexamethasone (RVd) |
| BortezomibBortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6. | Drug | Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd), Lenalidomide+Bortezomib+Dexamethasone (RVd) |
| DexamethasoneDexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16). | Drug | Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd), Lenalidomide+Bortezomib+Dexamethasone (RVd) |
| DaratumumabDaratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks. | Drug | Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd) |
Primary outcome
Percentage of Participants With Stringent Complete Response (sCR)
Time frame: 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 immunofluorescence or 2 to 4-color flow cytometry.
15 secondary outcomes
Percentage of Participants With Complete Response (CR) or Better
Time frame: 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)
Percentage of Participants With Overall Stringent Complete Response (sCR)
Time frame: 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)
Percentage of Participants With Overall Response Rate (ORR)
Time frame: 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)
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
Time frame: 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)
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Time frame: 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)
Duration of Complete Response or Better
Time frame: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)
Duration of Stringent Complete Response (sCR)
Time frame: From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)
Time to Stringent Complete Response (sCR)
Time frame: From randomization to the date of initial documentation of sCR (up to 5 years)
Time to Complete Response or Better
Time frame: From randomization to the date of initial documentation of CR (up to 5 years)
Time to Very Good Partial Response (VGPR) or Better
Time frame: From randomization to the date of initial documentation of VGPR or better (up to 5 years)
Time to Partial Response (PR) or Better
Time frame: From randomization to the date of initial documentation of PR or better (up to 5 years)
Progression-free Survival (PFS)
Time frame: From randomization to the date of first documented evidence of progressive disease or death (up to 5 years)
Overall Survival (OS)
Time frame: From randomization to the date of initial documentation of participant's death (up to 5 years)
Time to Progression (TTP)
Time frame: From randomization to the date of first documented evidence of progressive disease (up to 5 years)
Duration of Response
Time frame: From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39452950Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma. Future Oncol. 2025 Jan;21(1):25-49. doi: 10.1080/14796694.2024.2408909. Epub 2024 Oct 25.
- Derived from this study: PubMed 39287147Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, van de Donk NWCJ, Katodritou E, Schjesvold F, Balari AS, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P. A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma. Future Oncol. 2024;20(38):3043-3063. doi: 10.1080/14796694.2024.2394323. Epub 2024 Sep 17.
- Derived from this study: PubMed 38977707Chari A, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024 Jul 8;14(1):107. doi: 10.1038/s41408-024-01088-6.
- Derived from this study: PubMed 38649340Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
- Derived from this study: PubMed 38622840Silbermann R, Laubach J, Kaufman JL, Sborov DW, Reeves B, Rodriguez C, Chari A, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Orlowski RZ, Shain KH, Cowan AJ, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Health-related quality of life in transplant-eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient-reported outcomes from GRIFFIN. Am J Hematol. 2024 Jul;99(7):1257-1268. doi: 10.1002/ajh.27326. Epub 2024 Apr 15.
- Derived from this study: PubMed 37708911Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. 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. Lancet Haematol. 2023 Oct;10(10):e825-e837. doi: 10.1016/S2352-3026(23)00217-X. Epub 2023 Sep 11.
- Derived from this study: PubMed 36799429Nooka AK, Kaufman JL, Rodriguez C, Jakubowiak A, Efebera Y, Reeves B, Wildes T, Holstein SA, Anderson LD Jr, Badros A, Shune L, Chari A, Pei H, Cortoos A, Patel S, Lin TS, Richardson PG, Voorhees P. A plain language summary of daratumumab plus lenalidomide/bortezomib/dexamethasone in transplant-eligible Black patients with newly diagnosed multiple myeloma in the GRIFFIN study. Future Oncol. 2022 Dec;18(40):4443-4456. doi: 10.2217/fon-2022-0775. Epub 2023 Feb 17.
- Derived from this study: PubMed 36111391Sborov DW, Baljevic M, Reeves B, Laubach J, Efebera YA, Rodriguez C, Costa LJ, Chari A, Silbermann R, Holstein SA, Anderson LD Jr, Kaufman JL, Shah N, Pei H, Patel S, Cortoos A, Bartlett JB, Vermeulen J, Lin TS, Voorhees PM, Richardson PG. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022 Nov;199(3):355-365. doi: 10.1111/bjh.18432. Epub 2022 Sep 16.
- Derived from this study: PubMed 35985959Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.
- Derived from this study: PubMed 33606004Voorhees PM, Rodriguez C, Reeves B, Nathwani N, Costa LJ, Lutska Y, Bobba P, Hoehn D, Pei H, Ukropec J, Qi M, Lin TS, Richardson PG. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.
- Derived from this study: PubMed 32325490Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Murphy S, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin TS, Richardson PG. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945. doi: 10.1182/blood.2020005288.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
36 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenalidomide, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 36 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Stringent Complete Response (sCR) (time frame: From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02874742, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.