Back to results

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

Primary Purpose

Multiple Myeloma

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Daratumumab

Velcade

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Peking Union Medical College Hospital
Peking University First Hospital
Peking University People's Hospital
Peking University Third Hospital
The First Hospital of Jilin University
West China Hospital, Si Chuan University
Xinqiao Hospital of the Third Military Medical University
Fujian Meidical University Union Hospital
Guangdong Provincial People's Hospital
The First Affiliated Hospital, Sun Yat-sen University
Nanfang Hospital
First affiliated Hospital of Zhejiang University
First Affiliated Hospital, Medical School of Zhejiang University
Nanjing Drum Tower Hospital
Zhongda Hospital,Southeast University
Jiangsu Province Hospital
Shanghai Changzheng Hospital
Ruijin Hospital, Shanghai Jiao Tong University
First Affiliated Hospital, SooChow University
Tianjin cancer hospital
Tianjin Medical University General Hospital
Institute of Hematology & Blood Diseases Hospital
Tongji Hospital, Tongji Medical College of HUST
Tangdu Hospital
Henan Cancer Hospital
National Taiwan University Hospital
Tri-Service General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

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

Arm B: Velcade and Dexamethasone (Vd)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Time to Disease Progression (TTP)

TTP is defined as time from date of randomization to date of first documented evidence of PD. PD per IMWG criteria: Increase of 25 % from lowest response value in one of following: Serum M-component 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: difference between involved and uninvolved FLC levels (absolute increase must be greater than [>]10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow 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).

Overall Response Rate (ORR)

ORR is percentage of participants who achieve partial response (PR) or better (stringent complete response [sCR], complete response [CR], VGPR), according to the IMWG criteria, during the study or during follow up. PR: >=50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to <200 mg/24 hours; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved FLC levels; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; VGPR: serum and urine M-component detectable by immunofixation or >=90.0% reduction in serum M-protein and urine M-protein <100mg/24 hours; CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5.0% PCs in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs.

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

VGPR or better rate defined as the percentage of participants achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment. IMWG criteria for 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, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.

Time to Response

Time to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for response (PR or better rate). IMWG criteria for PR: >=50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to <200 mg/24 hours; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved FLC levels; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; VGPR: serum and urine M-component detectable by immunofixation or >=90.0% reduction in serum M-protein and urine M-protein <100mg/24 hours; CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5.0% PCs in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs.

Duration of Response

Duration of response will be calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of PD, as defined in the IMWG criteria. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria,If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30% in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

Overall Survival

Overall survival is measured from the date of randomization to the date of the participant's death.

Change From Baseline in Euro Quality of Life 5-Dimensions 5-Level (EQ-5D-5L) Utility Score

EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0), with higher values representing better general health status of the individual.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score

EORTC QLQ-C30 is a cancer-specific measure of health-related quality of life (HRQoL) that includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week (the past week). Scores are transformed to a 0 to 100 scale. A higher score for the global health status scale represents greater quality of life, a higher score for a functional scale represents greater functioning, and a higher score for a symptom scale/item represents more symptomatology/problems.

Full Information

NCT ID

NCT03234972

First Posted

July 27, 2017

Last Updated

October 10, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03234972

Brief Title

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

Official Title

A Randomized, Multicenter, Open-label, Phase 3 Study to Compare Daratumumab, Bortezomib, and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Chinese Subjects With Relapsed or Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 30, 2017 (Actual)

Primary Completion Date

October 7, 2019 (Actual)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

211 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Arm B: Velcade and Dexamethasone (Vd)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Daratumumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Velcade

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Time to Disease Progression (TTP)

Description

Time Frame

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

Title

Overall Response Rate (ORR)

Description

Time Frame

Approximately up to 4.5 years

Title

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

Description

Time Frame

Approximately up to 4.5 years

Title

Time to Response

Description

Time Frame

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)

Title

Duration of Response

Description

Time Frame

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)

Title

Overall Survival

Description

Overall survival is measured from the date of randomization to the date of the participant's death.

Time Frame

From date of randomization to the date of the participant's death (approximately up to 4.5 years)

Title

Change From Baseline in Euro Quality of Life 5-Dimensions 5-Level (EQ-5D-5L) Utility Score

Description

Time Frame

Baseline up to Weeks 8 and 16 post PD (Approximately up to 4.5 years)

Title

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score

Description

Time Frame

Baseline up to Weeks 8 and 16 post PD (Approximately up to 4.5 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

Peking Union Medical College Hospital

City

Beijing

ZIP/Postal Code

100032

Country

China

Facility Name

Peking University First Hospital

City

Beijing

ZIP/Postal Code

100034

Country

China

Facility Name

Peking University People's Hospital

City

Beijing

ZIP/Postal Code

100044

Country

China

Facility Name

Peking University Third Hospital

City

Beijing

ZIP/Postal Code

100083

Country

China

Facility Name

The First Hospital of Jilin University

City

Changchun

ZIP/Postal Code

130021

Country

China

Facility Name

West China Hospital, Si Chuan University

City

Chengdu

ZIP/Postal Code

610041

Country

China

Facility Name

Xinqiao Hospital of the Third Military Medical University

City

Chongqing

ZIP/Postal Code

400037

Country

China

Facility Name

Fujian Meidical University Union Hospital

City

Fuzhou

ZIP/Postal Code

350001

Country

China

Facility Name

Guangdong Provincial People's Hospital

City

Guangzhou

ZIP/Postal Code

510080

Country

China

Facility Name

The First Affiliated Hospital, Sun Yat-sen University

City

Guangzhou

ZIP/Postal Code

510080

Country

China

Facility Name

Nanfang Hospital

City

Guangzhou

ZIP/Postal Code

510515

Country

China

Facility Name

First affiliated Hospital of Zhejiang University

City

Hangzhou

ZIP/Postal Code

310020

Country

China

Facility Name

First Affiliated Hospital, Medical School of Zhejiang University

City

Hangzhou

ZIP/Postal Code

310020

Country

China

Facility Name

Nanjing Drum Tower Hospital

City

Nanjing

ZIP/Postal Code

210008

Country

China

Facility Name

Zhongda Hospital,Southeast University

City

Nanjing

ZIP/Postal Code

210009

Country

China

Facility Name

Jiangsu Province Hospital

City

Nanjing

ZIP/Postal Code

210029

Country

China

Facility Name

Shanghai Changzheng Hospital

City

Shanghai

ZIP/Postal Code

200003

Country

China

Facility Name

Ruijin Hospital, Shanghai Jiao Tong University

City

Shanghai

ZIP/Postal Code

200025

Country

China

Facility Name

First Affiliated Hospital, SooChow University

City

Suzhou

ZIP/Postal Code

215006

Country

China

Facility Name

Tianjin cancer hospital

City

Tianjin

ZIP/Postal Code

300040

Country

China

Facility Name

Tianjin Medical University General Hospital

City

Tianjin

ZIP/Postal Code

300052

Country

China

Facility Name

Institute of Hematology & Blood Diseases Hospital

City

Tianjin

ZIP/Postal Code

300320

Country

China

Facility Name

Tongji Hospital, Tongji Medical College of HUST

City

Wuhan

ZIP/Postal Code

430030

Country

China

Facility Name

Tangdu Hospital

City

Xian

ZIP/Postal Code

710038

Country

China

Facility Name

Henan Cancer Hospital

City

Zhengzhou

ZIP/Postal Code

450008

Country

China

Facility Name

National Taiwan University Hospital

City

Taipei

ZIP/Postal Code

10048

Country

Taiwan

Facility Name

Tri-Service General Hospital

City

Taipei

ZIP/Postal Code

11490

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

34108127

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs