A Study to Compare Daratumumab, Bortezomib, and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Chinese Participants With Relapsed or Refractory Multiple Myeloma

NCT03234972 | Completed Phase 3 DMC

• 2 other identifiers: CR10437854767414MMY3009
• Study Type: interventional
• Target: 213
• Locations: 2 countries
• Sites: 27

Brief Summary

The primary purpose of this study is to compare the efficacy of daratumumab when combined with Velcade (bortezomib) and dexamethasone (DVd) to that of Velcade and dexamethasone (Vd), in terms of progression free survival (PFS) in Chinese participants with relapsed or refractory multiple myeloma (MM).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is duration from date of randomization to either PD (as per international myeloma working group \[IMWG\] criteria) or death whichever occurs first. PD: Increase of 25 percent (%) from lowest response value in one of following: Serum M-component and urine M-component (absolute increase must be greater than or equal to \[\>=\]0.5 gram per deciliter \[g/dL\] and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be \>10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell (PC) percentage (absolute percentage must be \>=10%); 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).

  From the date of randomization to either progressive disease (PD) or death, whichever occurs first (approximately up to 4.5 years)

Secondary Outcomes (8)

• Time to Disease Progression (TTP)

  From the date of randomization to the date of first documented evidence of PD (approximately up to 4.5 years)

• Overall Response Rate (ORR)

  Approximately up to 4.5 years

• Percentage of Participants With a Very Good Partial Response (VGPR) or Better

  Approximately up to 4.5 years

• Time to Response

  From the date of randomization and the first efficacy evaluation that the participant has met all criteria for response (PR or better rate) (approximately up to 4.5 years)

• Duration of Response

  From the date of initial documentation of a response (PR or better rate) to the date of first documented evidence of PD (approximately up to 4.5 years)

Study Arms (2)

Arm A: Daratumumab, Velcade, and Dexamethasone (DVd)

EXPERIMENTAL

Participants will receive daratumumab weekly for the first 3 cycles, every 3 weeks (q3w) on Day 1 of Cycles 4-9 as an intravenous (IV) infusion at a dose of 16 milligram per kilogram (mg/kg) or will have the option to switch to daratumumab subcutaneously (SC) on Day 1 of any cycle, and then every 4 weeks (q4w) thereafter, Velcade at a dose of 1.3 milligram per square meter (mg/m\^2) subcutaneous (SC) on Days 1, 4, 8 and 11 of each 21-day cycle (up to 8 treatment cycles) and dexamethasone (Dex) orally (PO) at 20 milligram (mg) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the 8 Velcade treatment cycles.

Drug: Daratumumab; Drug: Velcade; Drug: Dexamethasone

Arm B: Velcade and Dexamethasone (Vd)

EXPERIMENTAL

Participants will receive Velcade SC at a dose of 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each 21-day cycle and Dex 20 mg PO on Days 1, 2, 4, 5, 8, 9, 11, 12 (up to 8 cycles). Participants who have sponsor-confirmed disease progression while being treated with Vd or on observation, will be offered the option for treatment with daratumumab monotherapy (16 mg/kg weekly for Cycles 1 and 2, every other week for Cycles 3 to 6, and every 4 weeks for Cycles 7 and onwards until disease progression, unacceptable toxicity, pregnancy, loss of follow-up, withdrawal of consent, or death \[each cycle is 28 days\]), if recommended by the site investigator.

Drug: Daratumumab; Drug: Velcade; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab will be administered on Day 1 of Cycles 4-9, and then q4w thereafter.

Arm A: Daratumumab, Velcade, and Dexamethasone (DVd); Arm B: Velcade and Dexamethasone (Vd)

Velcade DRUG

Velcade will be administered at a dose of 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each 21-day cycle.

Arm A: Daratumumab, Velcade, and Dexamethasone (DVd); Arm B: Velcade and Dexamethasone (Vd)

Dexamethasone DRUG

Dex will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 Velcade treatment cycles.

Arm A: Daratumumab, Velcade, and Dexamethasone (DVd); Arm B: Velcade and Dexamethasone (Vd)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented multiple myeloma (MM) as defined by the criteria: monoclonal plasma cells in the bone marrow greater than or equal to (\>=) 10 percent (%) at some point in the participant's disease course or presence of a biopsy-proven plasmacytoma
• Received at least 1 prior line of therapy for MM
• Documented evidence of progressive disease (PD) based on investigator's determination of response as defined by the International Myeloma Working Group (IMWG) criteria on or after their last regimen
• Achieved a response (partial response \[PR\] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

You may not qualify if:

• Received daratumumab or other anti-CD38 therapies
• Refractory to Velcade, or another proteasome inhibitor (PI), like ixazomib and carfilzomib (ie, participant had progression of disease while receiving Velcade therapy or within 60 days of ending Velcade therapy, or another PI, like ixazomib and carfilzomib, etc)
• Intolerant to Velcade (that is \[ie\], discontinued due to any adverse event while on Velcade treatment)
• Planning to undergo a stem cell transplant prior to progression of disease on this study, that is ie, these participants should not be enrolled in order to reduce disease burden prior to transplant
• History of malignancy (other than MM) within 3 years before the date of randomization

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (27)

Peking Union Medical College Hospital

Beijing, 100032, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Peking University People s Hospital

Beijing, 100044, China

Location

Peking University Third Hospital

Beijing, 100083, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital Si Chuan University

Chengdu, 610041, China

Location

Xinqiao Hospital of the Third Military Medical University

Chongqing, 400037, China

Location

Fujian Meidical University Union Hospital

Fuzhou, 350001, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510080, China

Location

The First Affiliated Hospital Sun Yat sen University

Guangzhou, 510080, China

Location

Nanfang Hospital

Guangzhou, 510515, China

Location

First Affiliated Hospital Medical School of Zhejiang University

Hangzhou, 310020, China

Location

First affiliated Hospital of Zhejiang University

Hangzhou, 310020, China

Location

Nanjing Drum Tower Hospital

Nanjing, 210008, China

Location

Zhongda Hospital Southeast University

Nanjing, 210009, China

Location

Jiangsu Province Hospital

Nanjing, 210029, China

Location

Shanghai Changzheng Hospital

Shanghai, 200003, China

Location

Ruijin Hospital Shanghai Jiao Tong University

Shanghai, 200025, China

Location

First Affiliated Hospital SooChow University

Suzhou, 215006, China

Location

Tianjin cancer hospital

Tianjin, 300040, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

Institute of Hematology and Blood Diseases Hospital

Tianjin, 300320, China

Location

Tongji Hospital, Tongji Medical College of HUST

Wuhan, 430030, China

Location

Tangdu Hospital

Xi'an, 710038, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Related Publications (2)

• Fu W, Li W, Hu J, An G, Wang Y, Fu C, Chen L, Jin J, Cen X, Ge Z, Cai Z, Niu T, Qi M, Gai X, Li Q, Liu W, Liu W, Yang X, Chen X, Lu J. Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. Clin Lymphoma Myeloma Leuk. 2023 Jan;23(1):e51-e58. doi: 10.1016/j.clml.2022.10.007. Epub 2022 Oct 23.

  PMID: 36402700 DERIVED

• Lu J, Fu W, Li W, Hu J, An G, Wang Y, Fu C, Chen L, Jin J, Cen X, Ge Z, Cai Z, Niu T, Qi M, Sun S, Gai X, Liu W, Liu W, Yang X, Huang X. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study. Clin Lymphoma Myeloma Leuk. 2021 Sep;21(9):e699-e709. doi: 10.1016/j.clml.2021.04.012. Epub 2021 Apr 24.

  PMID: 34108127 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 1, 2017
• Study Start: November 30, 2017
• Primary Completion: October 7, 2019
• Study Completion: February 27, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

CN (25); TW (2)