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)

NCT03217812 | Completed Phase 3 DMC

• 2 other identifiers: CR10834054767414MMY3011
• Study Type: interventional
• Target: 220
• Locations: 5 countries
• Sites: 44

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Very Good Partial Response (VGPR) or Better Rate at 6 Month After Last Participant First Dose

  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.

  At 6 months after last participant first dose (approximately up to 2.5 years)

• Very Good Partial Response (VGPR) or Better Rate at 3 Years After Last Participant First Dose

  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.

  At 3 years after last participant first dose (approximately up to 5 years)

Secondary Outcomes (15)

• Progression-Free Survival (PFS)

  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

  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)

• Overall Response Rate (ORR)

  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)

• Complete Response Rate

  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)

• Stringent Complete Response (sCR) Rate

  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)

Study Arms (2)

Treatment A: VMP Alone

ACTIVE COMPARATOR

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 (if serum creatine is greater than \[\>\]2 milligram per deciliter \[mg/dL\] at baseline, participants must be administrated 4.5 mg/m\^2 of melphalan, instead of 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; Drug: Melphalan; Drug: Prednisone

Treatment B: D-VMP

EXPERIMENTAL

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 (if serum creatine is \>2 mg/dL at baseline, participants must be administrated 4.5 mg/m\^2 of melphalan, instead of 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 or daratumumab Subcutaneously (SC) at the discretion of the investigator, 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; Drug: Melphalan; Drug: Prednisone; Drug: Daratumumab

Interventions

Velcade DRUG

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.

Also known as: Bortezomib

Treatment A: VMP Alone; Treatment B: D-VMP

Melphalan DRUG

Participants will receive melphalan 9 mg/m\^2 (if serum creatine is \>2 mg/dL at baseline, participants must be administrated 4.5 mg/m\^2 of melphalan, instead of 9 mg/m\^2), orally, once daily on Days 1 to 4 of each cycle up to Cycle 9 Treatment Arm A and B.

Treatment A: VMP Alone; Treatment B: D-VMP

Prednisone DRUG

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.

Treatment A: VMP Alone; Treatment B: D-VMP

Daratumumab DRUG

Participants will receive daratumumab 16 mg/kg as IV infusion or daratumumab SC, 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.

Also known as: JNJ-54767414

Treatment B: D-VMP

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (44)

Beijing Chaoyang Hospital

Beijing, 100020, China

Location

Peking Union Medical College Hospital

Beijing, 100032, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Chaoyang Hospital

Beijing, 100043, China

Location

Peking University Third Hospital

Beijing, 100083, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

The Third Xiangya Hospital, Central South University

Changsha, 410013, China

Location

West China Hospital Si Chuan University

Chengdu, 610041, China

Location

Second Affiliated Hospital of Army 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

Harbin medical university cancer hospital

Harbin, 150000, 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

Shanghai Zhongshan Hospital

Shanghai, 200032, China

Location

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200127, China

Location

First Affiliated Hospital SooChow University

Suzhou, 215006, China

Location

Tianjin cancer hospital

Tianjin, 300040, China

Location

Institute of Hematology and Blood Diseases Hospital

Tianjin, 300320, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000, 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

Queen Mary Hospital University of Hong Kong

Hong Kong, Hong Kong

Location

Hospital Ampang

Ampang, 68000, Malaysia

Location

Hospital Pulau Pinang

George Town, 10990, Malaysia

Location

Hospital Queen Elizabeth

Kota Kinabalu, 88586, Malaysia

Location

Inje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405-760, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 33305, Taiwan

Location

Related Publications (3)

• Fu W, Bang SM, Huang H, Kim K, Li W, An G, Lee JJ, Cai Z, Jin J, Wang Y, Chim CS, Carson R, Liu R, Zhao M, Chen X, Cui C, Hou J, Wang J. Health-related quality of life with daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible patients with newly diagnosed multiple myeloma: analysis of the phase 3 OCTANS study. Ann Hematol. 2025 May;104(5):2765-2776. doi: 10.1007/s00277-025-06303-3. Epub 2025 May 23.

  PMID: 40407887 DERIVED

• Fu W, Bang SM, Huang H, Kim K, Li W, An G, Lee JJ, Cai Z, Jin J, Wang Y, Chim CS, Carson R, Liu R, Zhao M, Chen X, Cui C, Hou J, Wang J. Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study. Ann Hematol. 2025 Jan;104(1):515-525. doi: 10.1007/s00277-024-05958-8. Epub 2024 Sep 4.

  PMID: 39227450 DERIVED

• Fu W, Bang SM, Huang H, Kim K, Li W, An G, Lee JJ, Cai Z, Jin J, Wang Y, Lin TL, Chim CS, Qi M, Wang J, Lu X, Song Y, Jia B, Yang X, Liu W, Zhou T, Yin L, Li Y, Zhang R, Hou J, Wang J. Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study. Clin Lymphoma Myeloma Leuk. 2023 Jun;23(6):446-455.e4. doi: 10.1016/j.clml.2023.02.009. Epub 2023 Mar 4.

  PMID: 37024420 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Melphalan; Prednisone; daratumumab

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; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

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 13, 2017
• First Posted: July 14, 2017
• Study Start: November 23, 2017
• Primary Completion: July 2, 2020
• Study Completion: March 8, 2024
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

CN (30); KR (7); TW (3); HK (1); MY (3)