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

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ClinicalTrials.gov Identifier: NCT03234972
Recruitment Status : Active, not recruiting
First Posted : August 1, 2017
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: Velcade Drug: Dexamethasone Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 211 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2017
Estimated Primary Completion Date : September 16, 2020
Estimated Study Completion Date : August 31, 2022


Arm Intervention/treatment
Experimental: Arm A: Daratumumab, Velcade, and Dexamethasone (DVd)
Participants will receive daratumumab as an intravenous (IV) infusion at a dose of 16 milligram per kilogram (mg/kg) weekly for the first 3 cycles, every 3 weeks (q3w) on Day 1 of Cycles 4-9, 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
Daratumumab will be administered as an IV infusion at a dose of 16 mg/kg weekly for the first 3 cycles, q3w on Day 1 of Cycles 4-9, and then q4w thereafter.

Drug: Velcade
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.

Drug: Dexamethasone
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.

Experimental: Arm B: Velcade and Dexamethasone (Vd)
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
Daratumumab will be administered as an IV infusion at a dose of 16 mg/kg weekly for the first 3 cycles, q3w on Day 1 of Cycles 4-9, and then q4w thereafter.

Drug: Velcade
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.

Drug: Dexamethasone
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 Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: From the date of randomization to either progressive disease (PD) or death, whichever occurs first (approximately up to 4.5 years) ]
    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 :
  1. Time to Disease Progression (TTP) [ Time Frame: From the date of randomization to the date of first documented evidence of PD (approximately up to 4.5 years) ]
    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).

  2. Overall Response Rate (ORR) [ Time Frame: Approximately up to 4.5 years ]
    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.

  3. Percentage of Participants With a Very Good Partial Response (VGPR) or Better [ Time Frame: Approximately up to 4.5 years ]
    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.

  4. Time to Response [ 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) ]
    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.

  5. Duration of Response [ 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) ]
    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.

  6. Overall Survival [ Time Frame: From date of randomization to the date of the participant's death (approximately up to 4.5 years) ]
    Overall survival is measured from the date of randomization to the date of the participant's death.

  7. Change From Baseline in Euro Quality of Life 5-Dimensions 5-Level (EQ-5D-5L) Utility Score [ Time Frame: Baseline up to Weeks 8 and 16 post PD (Approximately up to 4.5 years) ]
    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.

  8. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score [ Time Frame: Baseline up to Weeks 8 and 16 post PD (Approximately up to 4.5 years) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03234972


Locations
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China
Peking Union Medical College Hospital
Beijing, China, 100032
Peking University First Hospital
Beijing, China, 100034
Peking University People's Hospital
Beijing, China, 100044
Peking University Third Hospital
Beijing, China, 100083
The First Hospital of Jilin University
Changchun, China, 130021
West China Hospital, Si Chuan University
Chengdu, China, 610041
Xinqiao Hospital of the Third Military Medical University
Chongqing, China, 400037
Fujian Meidical University Union Hospital
Fuzhou, China, 350001
Guangdong General Hospital
Guangzhou, China, 510080
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, China, 510080
Nanfang Hospital
Guangzhou, China, 510515
First affiliated Hospital of Zhejiang University
Hangzhou, China, 310020
First Affiliated Hospital, Medical School of Zhejiang University
Hangzhou, China, 310020
Nanjing Drum Tower Hospital
Nanjing, China, 210008
Zhongda Hospital,Southeast University
Nanjing, China, 210009
Jiangsu Province Hospital
Nanjing, China, 210029
Shanghai Changzheng Hospital
Shanghai, China, 200003
Ruijin Hospital, Shanghai Jiao Tong University
Shanghai, China, 200025
First Affiliated Hospital, SooChow University
Suzhou, China, 215006
Institute of Hematology & Blood Diseases Hospital
Tianjin, China, China, 300320
Tianjin cancer hospital
Tianjin, China, 300040
Tianjin Medical University General Hospital
Tianjin, China, 300052
Tongji Hospital, Tongji Medical College of HUST
Wuhan, China, 430030
Tangdu Hospital
Xian, China, 710038
Henan Cancer Hospital
Zhengzhou, China, 450008
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 10048
Tri-Service General Hospital
Taipei, Taiwan, 11490
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03234972     History of Changes
Other Study ID Numbers: CR104378
54767414MMY3009 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 1, 2017    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: 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
Dexamethasone acetate
Bortezomib
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
Antineoplastic Agents, Hormonal