Clinical trial NCT03217812: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 or urine pregnancy tests 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 4.03
* 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
* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[Anti-HBc\] and/or antibodies to hepatitis B surface antigen \[Anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR

Primary outcomes:
measure: Very Good Partial Response (VGPR) or Better Rate at 6 Month After Last Participant First Dose
timeFrame: At 6 months after last participant first dose (approximately up to 2.5 years)
measure: Very Good Partial Response (VGPR) or Better Rate at 3 Years After Last Participant First Dose
timeFrame: At 3 years after last participant first dose (approximately up to 5 years)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Time to Next Treatment
timeFrame: 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)
measure: Overall Response Rate (ORR)
timeFrame: 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)
measure: Complete Response Rate
timeFrame: 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)
measure: Stringent Complete Response (sCR) Rate
timeFrame: 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)
measure: Time to Response
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Duration of Response
timeFrame: 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)
measure: Time to VGPR or Better Response
timeFrame: 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)
measure: Duration of VGPR or Better Response
timeFrame: 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)
measure: EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire
timeFrame: 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)
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (QLQ-C30) Questionnaire
timeFrame: 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)
measure: Number of Participants With Antibodies to Daratumumab
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: 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)
measure: Clinical Efficacy of D-VMP in High Risk Molecular Subgroups
timeFrame: 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)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chaoyang Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Chaoyang Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital, Central South University
city: Chengdu
country: China
facility: West China Hospital Si Chuan University
city: Chongqing
country: China
facility: Second Affiliated Hospital of Army Medical University
city: Fuzhou
country: China
facility: Fujian Meidical University Union Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Nanfang Hospital
city: Hangzhou
country: China
facility: First Affiliated Hospital Medical School of Zhejiang University
city: Hangzhou
country: China
facility: First affiliated Hospital of Zhejiang University
city: Harbin
country: China
facility: Harbin medical university cancer hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
city: ShangHai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
city: Suzhou
country: China
facility: First Affiliated Hospital SooChow University
city: Tianjin
country: China
facility: Tianjin cancer hospital
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of HUST
city: Xian
country: China
facility: Tangdu Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital University of Hong Kong
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: