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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02874742
Recruitment Status : Active, not recruiting
First Posted : August 22, 2016
Results First Posted : February 7, 2020
Last Update Posted : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief 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 autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Lenalidomide Drug: Bortezomib Drug: Dexamethasone Drug: Daratumumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 29, 2016
Actual Primary Completion Date : January 25, 2019
Estimated Study Completion Date : January 25, 2022


Arm Intervention/treatment
Experimental: Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd)
Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab.
Drug: Lenalidomide
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.

Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.

Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).

Drug: Daratumumab
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.

Experimental: Lenalidomide+Bortezomib+Dexamethasone (RVd)
Participants will receive lenalidomide, bortezomib and dexamethasone.
Drug: Lenalidomide
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.

Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.

Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).




Primary Outcome Measures :
  1. 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 have 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 PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.


Secondary Outcome Measures :
  1. Percentage of Participants With Overall Complete Response (CR) [ Time Frame: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months) ]
    Overall CR rate is defined as the percentage of participants who achieve CR, 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.

  2. 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 during maintenance treatment (up to 24 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.

  3. 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 during maintenance treatment (up to 24 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 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.

  4. 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 during maintenance treatment (up to 24 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.

  5. 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) ]
    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.

  6. Duration of Complete Response [ Time Frame: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 2 years and 5 months) ]
    Duration of CR is the duration from the date of initial documentation of a CR 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 milligram [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 cell (PC) proliferative disorder.

  7. 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 2 years and 5 months) ]
    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.

  8. Time to Stringent Complete Response (sCR) [ Time Frame: From randomization to the date of initial documentation of sCR (up to 2 years and 5 months) ]
    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.

  9. Time to Complete Response or Better [ Time Frame: From randomization to the date of initial documentation of CR (Up to 2 years and 5 months) ]
    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.

  10. 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 2 years and 5 months) ]
    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.

  11. Time to Partial Response (PR) or Better [ Time Frame: From randomization to the date of initial documentation of PR or better (up to 2 years and 5 months) ]
    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.

  12. Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]
    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.

  13. Overall Survival (OS) [ Time Frame: From randomization to the date of initial documentation of participant's death (up to 2 years and 5 months) ]
    OS is measured from the date of randomization to the date of the participant's death.

  14. Time to Progression (TTP) [ Time Frame: From randomization to the date of first documented evidence of progressive disease (up to 2 years and 5 months) ]
    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.

  15. 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 2 years and 5 months) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02874742


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, California
Duarte, California, United States
La Jolla, California, United States
Los Angeles, California, United States
San Francisco, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Orlando, Florida, United States
Tampa, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Kansas
Westwood, Kansas, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
Worcester, Massachusetts, United States
United States, Michigan
Detroit, Michigan, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New York
Buffalo, New York, United States
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
Charlotte, North Carolina, United States
Durham, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Columbus, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Abington, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Washington
Seattle, Washington, United States
Spokane, Washington, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] January 10, 2019
Statistical Analysis Plan  [PDF] February 27, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02874742    
Other Study ID Numbers: CR108195
54767414MMY2004 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 22, 2016    Key Record Dates
Results First Posted: February 7, 2020
Last Update Posted: August 14, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Lenalidomide
Bortezomib
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors