Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | PHASE3 | COMPLETED | 220 | — | — | Nov 23, 2017 | Mar 8, 2024 | Apr 25, 2024 | 44 | China, Hong Kong +3 |
| NCT02195479 | A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma | PHASE3 | COMPLETED | 706 | — | — | Dec 9, 2014 | Aug 7, 2024 | Aug 22, 2025 | 160 | United States, Argentina +22 |
| NCT00388635 | Velcade-Melphalan-Prednisone in Older Untreated Multiple Myeloma Patients. | PHASE1 | COMPLETED | 60 | — | — | Apr 1, 2004 | Dec 1, 2008 | Jan 11, 2011 | 19 | Spain |
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.
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.
PFS: duration from date of randomization to progressive disease (PD)/death, whichever occurs first. PD per IMWG criteria-Increase of 25% from lowest response value in one of following: Serum M-component (absolute increase \>=0.5 grams per deciliter \[g/dL\]); Urine M-component (absolute increase \>=200 milligrams \[mg\]/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase \>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow Plasma cells (PC) percentage (%) (absolute % \>=10%); Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| Treatment Arm A (VMP Alone) | ACTIVE_COMPARATOR | Participants will receive velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous 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. |
| Treatment Arm 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, 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 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. On days when daratumumab is given, dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute, and prednisone 60 mg/m2 once daily will be given on Days 2-4. Following amendment 7, participants will have the option to switch to daratumumab subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator. |
| Name | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Daratumumab IV | DRUG | Participants will receive daratumumab 16 mg/kg as intravenous 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 until the end of study . |
| Dexamethasone | DRUG | Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute. |
| Daratumumab SC | DRUG | Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC. |
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, ...