Multiple MyelomaPhase 3NCT03217812
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)
A Phase 3 study testing Velcade, Melphalan and Prednisone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 44 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Velcade, Melphalan and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 44 sitesin 5 countries
- Study dates
- 23 Nov 2017to 8 Mar 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
44 sites in 5 countries.
44 sites in 5 countries
China30 sites
Beijing Chaoyang Hospital
Beijing, 100020
Peking Union Medical College Hospital
Beijing, 100032
Peking University First Hospital
Beijing, 100034
Beijing Chaoyang Hospital
Beijing, 100043
Peking University Third Hospital
Beijing, 100083
The First Hospital of Jilin University
Changchun, 130021
The Third Xiangya Hospital, Central South University
Changsha, 410013
West China Hospital Si Chuan University
Chengdu, 610041
Second Affiliated Hospital of Army Medical University
Chongqing, 400037
Fujian Meidical University Union Hospital
Fuzhou, 350001
Guangdong Provincial People's Hospital
Guangzhou, 510080
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, 510080
Nanfang Hospital
Guangzhou, 510515
First Affiliated Hospital Medical School of Zhejiang University
Hangzhou, 310020
First affiliated Hospital of Zhejiang University
Hangzhou, 310020
Harbin medical university cancer hospital
Harbin, 150000
Nanjing Drum Tower Hospital
Nanjing, 210008
Zhongda Hospital Southeast University
Nanjing, 210009
Jiangsu Province Hospital
Nanjing, 210029
Shanghai Changzheng Hospital
Shanghai, 200003
Ruijin Hospital, Shanghai Jiao Tong University
Shanghai, 200025
Shanghai Zhongshan Hospital
Shanghai, 200032
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, 200127
First Affiliated Hospital SooChow University
Suzhou, 215006
Tianjin cancer hospital
Tianjin, 300040
Institute of Hematology and Blood Diseases Hospital
Tianjin, 300320
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, 325000
Tongji Hospital, Tongji Medical College of HUST
Wuhan, 430030
Tangdu Hospital
Xi'an, 710038
Henan Cancer Hospital
Zhengzhou, 450008
South Korea7 sites
Inje University Busan Paik Hospital
Busan, 47392
Gachon University Gil Medical Center
Incheon, 405-760
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128
Seoul National University Bundang Hospital
Seongnam-si, 13620
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, 06591
Ulsan University Hospital
Ulsan, 44033
Malaysia3 sites
Hospital Ampang
Ampang, 68000
Hospital Pulau Pinang
George Town, 10990
Hospital Queen Elizabeth
Kota Kinabalu, 88586
Taiwan3 sites
National Taiwan University Hospital
Taipei, 10048
Taipei Veterans General Hospital
Taipei, 11217
Chang Gung Memorial Hospital
Taoyuan, 33305
About this study
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)
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
- Being tested
- Velcade, Melphalan, Prednisone, Daratumumab
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VelcadeDrug
Also called Bortezomib
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.
MelphalanDrug
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.
PrednisoneDrug
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.
DaratumumabDrug
Also called JNJ-54767414
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Velcade; Drug: Melphalan; Drug: Prednisone; Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At 3 years after last participant first dose (approximately up to 5 years)
Secondary outcomes (15)
Progression-Free Survival (PFS)
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.
Measured: 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
Time to next treatment is defined as the time from randomization to the start of the next-line treatment.
Measured: 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)
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.
Measured: 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
Complete response based on IMWG criteria is defined as: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow.
Measured: 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
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.
Measured: 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)
Time to Response
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.
Measured: 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 Survival (OS)
The OS is defined as the time from the date of randomization to the date of the participant's death.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire
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).
Measured: 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)
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (QLQ-C30) Questionnaire
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.
Measured: 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)
Number of Participants With Antibodies to Daratumumab
Number of participants with antibodies to daratumumab will be analysed.
Measured: 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 Adverse Events (AEs) as a Measure of Safety and Tolerability
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.
Measured: 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 of D-VMP in High Risk Molecular Subgroups
Clinical efficacy will be analyzed in high risk molecular subgroups between DVMP and VMP.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2017
- Study start23 Nov 2017
- Primary completion2 Jul 2020
- Study completion8 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03217812
- Sponsor's protocol ID
- CR108340
- Other IDs
- 54767414MMY3011
- Status last verified
- Apr 2024
- First submitted
- 13 Jul 2017
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40407887Fu 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.
PubMed 39227450Fu 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.
PubMed 37024420
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03217812
- Acronym / sponsor ID
- CR108340
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Nov 2017 (actual)
- Primary completion
- 2 Jul 2020 (actual)
- Study completion
- 8 Mar 2024 (actual)
- First posted
- 14 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A: VMP Alone | Active comparator | Drug: Velcade, Drug: Melphalan, Drug: PrednisoneParticipants 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. |
| Treatment B: D-VMP | Experimental | Drug: Velcade, Drug: Melphalan, Drug: Prednisone, Drug: DaratumumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VelcadeAlso: BortezomibParticipants 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. | Drug | Treatment A: VMP Alone, Treatment B: D-VMP |
| MelphalanParticipants 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. | Drug | Treatment A: VMP Alone, Treatment B: D-VMP |
| PrednisoneParticipants 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 | Treatment A: VMP Alone, Treatment B: D-VMP |
| DaratumumabAlso: JNJ-54767414Participants 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. | Drug | Treatment B: D-VMP |
Primary outcome
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.
15 secondary outcomes
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)
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)
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)
Complete Response 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)
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)
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)
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)
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)
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)
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)
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)
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)
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 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)
Clinical Efficacy of D-VMP in High Risk Molecular Subgroups
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Derived from this study: PubMed 40407887Fu 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.
- Derived from this study: PubMed 39227450Fu 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.
- Derived from this study: PubMed 37024420Fu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
44 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Velcade, Melphalan and Prednisone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 44 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in China, South Korea, Malaysia, Taiwan, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03217812, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2024.