This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified August 2017 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT03217812
First received: July 13, 2017
Last updated: August 24, 2017
Last verified: August 2017
  Purpose
The purpose of this study is to determine if the addition of daratumumab to VELCADE-melphalan-prednisone (VMP) will improve very good partial response (VGPR) or better compared with VMP alone.

Condition Intervention Phase
Multiple Myeloma Drug: Velcade Drug: Melphalan Drug: Prednisone Drug: Daratumumab Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region)

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Very Good Partial Response (VGPR) or Better Rate at 6 Month After Last Participant First Dose [ Time Frame: At 6 months after last participant first dose (approximately up to 2.5 years) ]
    The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according to the international myeloma working group (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 greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and less than (<) 5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence or 2- to 4 color flow cytometry.

  • Very Good Partial Response (VGPR) or Better Rate at 3 Years After Last Participant First Dose [ Time Frame: At 3 years after last participant first dose (approximately up to 5 years) ]
    The VGPR or better rate, defined as the proportion 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% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence or 2- to 4 color flow cytometry.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The PFS is defined as time from date of randomization to either Progressive disease (PD), death, whichever occurs first according to IMWG criteria. IMWG criteria for PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  • Time to Next Treatment [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Time to next treatment is defined as the time from randomization to the start of the next-line treatment.

  • Overall Response Rate (ORR) [ Time Frame: At 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to IMWG criteria, during or after study treatment. IMWG criteria: >=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 plasma cells (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.

  • Stringent Complete Response (sCR) Rate [ Time Frame: At 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The sCR rate is defined as the proportion of participants achieving CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry (IHC), immunofluorescence, 2‑4 color flow cytometry.

  • Time to Response [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Time to response, defined as the time between randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. 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 (OS) [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The OS is defined as the time from the date of randomization to the date of the participant's death.

  • Duration of Response [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Duration of response is time from the date of initial documentation of response (PR or better) to the date of first documented evidence of PD, as defined by IMWG criteria. IMWG criteria for PD: Increase of 25% from lowest response value in any one of the following: Serum M-component (absolute increase must be >=0.5 g/dL, Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >10 milligram per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC%(absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia ( serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  • Time to VGPR or Better Response [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Time to VGPR or better response defined as the time between randomization and the first efficacy evaluation that the participant has met all criteria for VGPR or better in responders. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence or 2- to 4 color flow cytometry.

  • Duration of VGPR or Better Response [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Duration of VGPR or better response is calculated from the date of initial documentation of the first (VGPR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence or 2- to 4 color flow cytometry.

  • EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire [ Time Frame: At 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).

  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (QLQ-C30) Questionnaire [ Time Frame: At 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status scale, 3 symptom scales (fatigue, pain, nausea/vomiting) and 6 single items (dyspnea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). The recall period is 1 week (the past week). Scores are transformed to a 0 to 100 scale. Higher score=better level of functioning or greater degree of symptoms.

  • Number of Participants With Antibodies to Daratumumab [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Number of participants with antibodies to daratumumab will be analysed.

  • Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability. [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

  • Clinical Efficacy of D-VMP in High Risk Molecular Subgroups Compared to VMP Alone [ Time Frame: Up to 6 months after last participant first dose (approximately up to 2.5 years) and 3 years after last participant first dose (approximately up to 5 years) ]
    Clinical efficacy will be compared in high risk molecular subgroups between DVMP and VMP.


Estimated Enrollment: 192
Anticipated Study Start Date: October 23, 2017
Estimated Study Completion Date: August 31, 2022
Estimated Primary Completion Date: January 17, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment A: VMP Alone
Participants will receive Velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m^2 orally, once daily (on Days 1 to 4) and prednisone 60 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.
Drug: Velcade
Participants will receive velcade 1.3 mg/m^2, SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9 of Treatment Arm A and B.
Other Name: Bortezomib
Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9 Treatment Arm A and B.
Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9 Treatment Arm A and B.
Experimental: Treatment B: D-VMP
Participants will receive Velcade 1.3 mg/m^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m^2, orally, once daily (on Days 1-4) and prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. In addition participants will also receive daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycles 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or the end of study. Participants will receive pre-infusion medications before each daratumumab infusion.
Drug: Velcade
Participants will receive velcade 1.3 mg/m^2, SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9 of Treatment Arm A and B.
Other Name: Bortezomib
Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9 Treatment Arm A and B.
Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9 Treatment Arm A and B.
Drug: Daratumumab
Participants will receive daratumumab 16 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or the end of study in Treatment Arm B.
Other Name: JNJ-54767414

  Eligibility

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

Inclusion Criteria:

  • Documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytomas, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol
  • Newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >= 65 years, or in participants less than (<) 65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Meet the clinical laboratory criteria as specified in the protocol
  • A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

  • Primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
  • Waldenstrom's disease, or other conditions in which Immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
  • Prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 milligram per day (mg/day) for 4 days) of corticosteroids before treatment
  • Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
  • History of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
  • Radiation therapy within 14 days of randomization
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03217812

Contacts
Contact: Study contact 844-434-4210 JNJ.CT@sylogent.com

Locations
China
Beijing Chaoyang Hospital Not yet recruiting
Beijing, China, 100020
Peking Union Medical College Hospital Not yet recruiting
Beijing, China, 100032
Peking University First Hospital Not yet recruiting
Beijing, China, 100034
Peking University People's Hospital Not yet recruiting
Beijing, China, 100044
Peking University Third Hospital Not yet recruiting
Beijing, China, 100083
The First Hospital of Jilin University Not yet recruiting
Changchun, China, 130021
West China Hospital, Si Chuan University Not yet recruiting
Chengdu, China, 610041
Xinqiao Hospital of the Third Military Medical University Not yet recruiting
Chongqing, China, 400037
Fujian Meidical University Union Hospital Not yet recruiting
Fuzhou, China, 350001
Guangdong General Hospital Not yet recruiting
Guangzhou, China, 510080
Nanfang Hospital Not yet recruiting
Guangzhou, China, 510515
First affiliated Hospital of Zhejiang University Not yet recruiting
Hangzhou, China, 310020
First Affiliated Hospital, Medical School of Zhejiang University Not yet recruiting
Hangzhou, China, 310020
Zhongda Hospital,Southeast University Not yet recruiting
Nanjing, China, 210009
Jiangsu Province Hospital Not yet recruiting
Nanjing, China, 210029
The Affiliated Hospital of Medical College Qingdao University Not yet recruiting
Qingdao, China, 266003
Shanghai Changzheng Hospital Not yet recruiting
Shanghai, China, 200003
Ruijin Hospital, Shanghai Jiao Tong University Not yet recruiting
Shanghai, China, 200025
Shanghai Zhongshan Hospital Not yet recruiting
Shanghai, China, 200032
First Affiliated Hospital, SooChow University Not yet recruiting
Suzhou, China, 215006
Tongji Hospital, Tongji Medical College of HUST Not yet recruiting
Wuhan, China, 430030
Tangdu Hospital Not yet recruiting
Xian, China, 710038
Korea, Republic of
Inje University Busan Paik Hospital Not yet recruiting
Busan, Korea, Republic of, 47392
Chonnam National University Hwasun Hospital Not yet recruiting
Hwasun Gun, Korea, Republic of, 58128
Seoul National University Bundang Hospital Not yet recruiting
Seongnam-Si, Korea, Republic of, 13620
Taiwan
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 10048
Chang Gung Memorial Hospital Not yet recruiting
Taoyuan, Taiwan, 33305
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03217812     History of Changes
Other Study ID Numbers: CR108340
54767414MMY3011 ( Other Identifier: Janssen Research & Development, LLC )
Study First Received: July 13, 2017
Last Updated: August 24, 2017

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:
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
Prednisone
Daratumumab
Bortezomib
Melphalan
Antibodies, Monoclonal
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 21, 2017