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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

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ClinicalTrials.gov Identifier: NCT02874742
Recruitment Status : Active, not recruiting
First Posted : August 22, 2016
Last Update Posted : August 19, 2019
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 : 222 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. Stringent complete response (sCR) Rate [ Time Frame: From randomization to 150 days Post-ASCT ]
    sCR rate by the end of post-ASCT consolidation treatment, defined as the proportion of participants who have achieved sCR, according to the IMWG criteria, by the end of post-ASCT consolidation treatment.


Secondary Outcome Measures :
  1. Overall Complete Response (CR) Rate [ Time Frame: From randomization to following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and maintenance treatment (up to 24 months) ]
    Overall CR rate is defined as the proportion of participants who achieve CR, according to the IMWG criteria, by the respective time point.

  2. Overall Stringent complete response (sCR) Rate [ Time Frame: From randomization to following: induction treatment, ASCT and maintenance treatment (up to 24 months) ]
    Overall sCR rate is defined as the proportion of participants who achieve sCR, according to the IMWG criteria, by the respective time point.

  3. Overall response rate (ORR) [ Time Frame: From randomization to following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and maintenance treatment (up to 24 months) ]
    ORR is defined as the proportion of participants who achieve PR or better, according to the IMWG criteria, by the respective time point.

  4. Proportion of Participants who Achieve Very Good Partial Response (VGPR) or Better [ Time Frame: From randomization to following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and maintenance treatment (up to 24 months) ]
    VGPR or better rate is defined as the proportion of participants achieving VGPR or better, according to the IMWG criteria, by the respective time point.

  5. Proportion of Participants With Minimal Residual Disease (MRD) [ Time Frame: From randomization to following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and maintenance treatment (up to 24 months) ]
    Minimal residual disease negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point.

  6. Duration of Complete Response (CR) [ Time Frame: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 3 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, or relapse from CR.

  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 3 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.

  8. Time to Complete Response (CR) [ Time Frame: From randomization to the date of initial documentation of CR (up to 3 years and 5 months) ]
    Time to CR is the duration from the date of randomization to the date of initial documentation of CR, which was confirmed by a repeated measurement as required by the IMWG criteria.

  9. Time to Stringent Complete Response (sCR) [ Time Frame: From randomization to the date of initial documentation of sCR (up to 3 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.

  10. Time to Very Good Partial Response (VGPR) or better [ Time Frame: From randomization to the date of initial documentation of VGPR (up to 3 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 VGPR (up to 3 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. Time to Progression (TTP) [ Time Frame: From randomization to the date of first documented evidence of progressive disease (up to 3 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.

  13. Progression-Free Survival (PFS) [ Time Frame: From the date of randomization to the date of first documented evidence of progressive disease or death (up to 3 years and 5 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.

  14. Overall Survival (OS) [ Time Frame: From the date of randomization to the date of the participant's death (up to 3 years and 5 months) ]
    OS is measured from the date of randomization to the date of the participant's death.

  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 disease (up to 3 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.



Information from the National Library of Medicine

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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


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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02874742     History of Changes
Other Study ID Numbers: CR108195
54767414MMY2004 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 22, 2016    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
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
Dexamethasone acetate
Lenalidomide
Bortezomib
Daratumumab
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists