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

NCT ID: NCT02874742

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-29
• Study Completion Date: 2022-04-08

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd)

Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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.

Bortezomib

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Daratumumab

Intervention Type: DRUG

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.

Lenalidomide+Bortezomib+Dexamethasone (RVd)

Participants will receive lenalidomide, bortezomib and dexamethasone.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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.

Bortezomib

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Bortezomib

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Duarte, California, United States

La Jolla, California, United States

Los Angeles, California, United States

San Francisco, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Orlando, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Westwood, Kansas, United States

New Orleans, Louisiana, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

Detroit, Michigan, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Buffalo, New York, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Winston-Salem, North Carolina, United States

Columbus, Ohio, United States

Portland, Oregon, United States

Abington, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

Salt Lake City, Utah, United States

Seattle, Washington, United States

Spokane, Washington, United States

Milwaukee, Wisconsin, United States

Countries

United States

References

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54767414MMY2004

Identifier Type: OTHER

Identifier Source: secondary_id

CR108195

Identifier Type: -

Identifier Source: org_study_id