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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07624513 | Determination 2 - Isatuximab, Iberdomide, Bortezomib and Dexamethasone Induction, Followed by Risk- and Response-Adapted Consolidation and Maintenance Therapy, in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma | PHASE3 | NOT YET_RECRUITING | 720 | — | — | Jun 8, 2026 | Mar 1, 2038 | Jun 3, 2026 | 3 | United States |
| NCT05804032 | Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Patients With Newly Diagnosed Multiple Myeloma | PHASE3 | COMPLETED | 514 | — | — | Apr 14, 2023 | Jan 30, 2026 | Feb 18, 2026 | 91 | Austria, Germany |
| NCT04934475 | MInimal Residual Disease Adapted Strategy | PHASE3 | ACTIVE NOT_RECRUITING | 791 | — | — | Dec 8, 2021 | Sep 30, 2028 | Nov 7, 2024 | 73 | Belgium, France +1 |
| NCT04751877 | Multicenter Open Label Phase 3 Study of Isatuximab Plus Lenalidomide and Dexamethasone With/Without Bortezomib in the Treatment of Newly Diagnosed Non Frail Transplant Ineligible Multiple Myeloma Elderly Patients (≥ 65; < 80 Years). | PHASE3 | ACTIVE NOT_RECRUITING | 270 | — | — | Jul 17, 2021 | Aug 17, 2027 | Feb 10, 2026 | 1 | France |
| NCT06517017 | Use of Isatuximab, Dexamethasone and Lenalidomide in a Go-Slow Fashion for Ultra-Frail Patients With Multiple Myeloma | PHASE2 | RECRUITING | 40 | — | — | Oct 9, 2025 | Nov 1, 2027 | Nov 28, 2025 | 1 | United States |
| NCT05911321 | Isa-Pom-Dex in Elderly/Frail Subjects With RRMM | PHASE2 | ACTIVE NOT_RECRUITING | 6 | — | — | Dec 5, 2023 | Mar 26, 2028 | Jun 8, 2026 | 2 | United States |
| NCT05776979 | Post-Transplant Maintenance Therapy With Isatuximab Plus Lenalidomide for High-Risk Multiple Myeloma Patients | PHASE2 | RECRUITING | 61 | — | — | Aug 17, 2023 | Dec 31, 2027 | Jun 8, 2026 | 1 | United States |
| NCT05123131 | Isa-RVD Study in Patients With Newly Diagnosed Multiple Myeloma | PHASE2 | ACTIVE NOT_RECRUITING | 54 | — | — | Apr 1, 2022 | Dec 15, 2027 | Jul 8, 2025 | 5 | Denmark, Ireland |
| NCT05145400 | Isa-Rd for Frail and/or Much Older Patients With Newly Diagnosed Multiple Myeloma | PHASE2 | RECRUITING | 50 | — | — | Feb 18, 2022 | May 28, 2033 | Jun 2, 2026 | 5 | United States |
| NCT04653246 | Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM | PHASE2 | ACTIVE NOT_RECRUITING | 52 | — | — | Jul 13, 2021 | Jan 13, 2029 | Apr 30, 2026 | 1 | United States |
| NCT04430894 | KRDI in Transplant-Eligible MM | PHASE2 | ACTIVE NOT_RECRUITING | 50 | — | — | Jul 10, 2020 | Dec 30, 2026 | Jun 3, 2026 | 3 | United States |
| NCT02332850 | Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma | PHASE1 | ACTIVE NOT_RECRUITING | 83 | — | — | Jan 21, 2015 | Dec 31, 2025 | May 1, 2025 | 6 | United States, Canada |
sMRD-negative CR rate is defined as the proportion of participants who sustain MRD negativity at a minimum 10\^-5 sensitivity assessed by next-generation sequencing (NGS) during the time of confirmed CR or better response per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC).
MRD-negative CR rate is defined as the proportion of participants who achieve MRD negativity at a minimum 10\^-5 sensitivity assessed by NGS during the time of confirmed CR or better response per IMWG-URC.
Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).
For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for robustness of the results.
Proportion of patients with a reduction tumoral mass ≥50 percent who experience a Minimal Residual Disease (MRD) 10-5 per IMWG (International Myeloma Working Group) criteria.
Assess the feasibility of approach incorporating the use of isatuximab and dexamethasone with the subsequent addition of lenalidomide from the third cycle onwards in ultra-frail patients with myeloma
Overall response rate (ORR) is defined as the percentage of participants achieving a partial response or better (≥PR) per IMWG criteria. The number and percentage of participants achieving at least a partial response were reported. Complete response (CR) requires negative serum and urine immunofixation, disappearance of plasmacytomas, and \<5% bone marrow plasma cells; stringent complete response (sCR) requires CR plus a normal free light chain ratio and no clonal plasma cells in bone marrow. Very good partial response (VGPR) is defined as M-protein detectable by immunofixation but not electrophoresis, or a ≥90% reduction in serum M-protein with urine M-protein \<100 mg/24h. Partial response (PR) is defined as a ≥50% reduction in serum M-protein and a ≥90% reduction in 24-hour urine M-protein (or to \<200 mg/24h), with a ≥50% reduction in plasmacytomas if present at baseline.
To evaluate the Very Good Partial Response (VGPR) or better rate by the end of two cycles of induction treatment, defined as the proportion of patients who have achieved VGPR, according to International Myeloma Working Group (IMWG) criteria, by the end of two cycles of induction treatment.
proportion of patients who have achieved VGPR or better, according to International Myeloma Working Group (IMWG) criteria (Kumar 2016), by the end of two cycles of induction treatment
Percentage of patients who achieved a complete response (CR) or stringent CR (sCR) per International Myeloma Working Group (IMWG) Uniform Response criteria after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI). IMWG criteria define a CR as "Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow" and an sCR as "CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence."
Treatment-related Adverse events resulting in a DLT will be summarized by maximum toxicity grade for each dose level of isatuximab.
The MTD is defined as the dose level below the lowest dose that induces dose- limiting toxicity in at least one-third of patients Adverse events will be summarized by maximum toxicity grade and by dose level for each ARM of the trial using NCI CTCAE v4.03
Overall response rate (ORR) as define by the International Myeloma Working Group (IMWG) uniform response criteria of patients obtaining Stringent Complete Remission (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), or Minimal Remission (MR)
| Arm | Type | Description |
|---|---|---|
| Arm A (Induction and screening) | OTHER | All enrolled participants begin with Step 1 induction for 8 28-day cycles before end-of-induction cohort assignment. PBSC mobilization/collection is planned between Cycles 4-6 for participants without progression. End-of-induction MRD/response and risk status determine whether participants proceed to Cohort 1 or Cohort 2. |
| Arm B (Cohort 1 Maintenance Therapy Part 1) | OTHER | Participants assigned to Cohort 1 enter Arm B and receive isatuximab + iberdomide maintenance for 36 cycles. Maintenance should begin within 28 days of the last induction cycle. |
| Arm C: Cohort 1 Maintenance Therapy (Part 2), Single-Agent Iberdomide | OTHER | After completion of Arm B, participants with MRD-negative CR status at Step 3 are assigned to Arm C and continue single-agent iberdomide until progression. Isatuximab is not administered in Arm C. |
| Arm D: Cohort 1 Maintenance Therapy (Part 2), Iberdomide + Isatuximab | OTHER | After completion of Arm B, participants with MRD-positive or MRD-indeterminate disease, or \<VGPR at Step 3 evaluation (unless PD), continue iberdomide + isatuximab until progression. |
| Arm E: Cohort 2 Randomized Consolidation and Maintenance (HDM-ASCT Strategy) | ACTIVE_COMPARATOR | Eligible Cohort 2 participants are randomized to Arm E: HDM-ASCT consolidation followed by isatuximab + iberdomide maintenance until progression. The protocol identifies Arm E as the control arm and describes HDM-ASCT-based therapy as the SOC comparator for Cohort 2. Consolidation should begin preferably within 30 days, and no later than 42 days, after induction completion. Maintenance begins 60-110 days after PBSC infusion. |
| Arm F: Cohort 2 Randomized Consolidation and Maintenance (Linvoseltamab Strategy) | EXPERIMENTAL | Eligible Cohort 2 participants are randomized to Arm F: linvoseltamab consolidation for 8 cycles followed by isatuximab + iberdomide maintenance until progression. The protocol explicitly identifies Arm F as the experimental arm and hypothesizes superior efficacy versus Arm E. Maintenance should begin within 2-4 weeks after the last linvoseltamab dose. |
| Arm G: Cohort 2 Non-randomized 3-Drug Maintenance | OTHER | Participants in Cohort 2 who do not meet criteria for consolidation therapy may enter Arm G. SR MRD-indeterminate participants may also enter Arm G or, with Sponsor-Investigator approval, may be randomized in Cohort 2. Arm G is a 3-drug maintenance regimen continued in 28-day cycles until progression. The protocol explicitly states that dexamethasone is excluded from Arm G. |
| Arm A - Intravenous isatuximab | ACTIVE_COMPARATOR | Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation. |
| Arm B - Subcutaneous isatuximab | EXPERIMENTAL | Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation. |
| MRD Standard-risk patients (post induction MRD <10-5, MRD SR) (1:1 Randomization) : Arm A | EXPERIMENTAL | Arm A: consolidation with 6 additional cycles of Isa-KRD (cycles 7 to 12; 28-day cycle; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone): * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 12) * Carfilzomib: 56 mg/m2 I.V on days 1, 8 and 15 (cycles 7 to 12) * Lenalidomide: 25 mg per day orally from days 1 to 21 * Dexamethasone: 40 mg orally on day 1, 8, 15, 22 |
| MRD Standard-risk patients (post induction MRD <10-5, MRD SR) (1:1 Randomization): Arm B | EXPERIMENTAL | Arm B: consolidation with ASCT followed by 2 cycles of Isa-KRD (cycles 7 and 8; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone; 28-day cycle) Melphalan 200 mg/m2 followed by autologous stem cell transplantation (please refer to section 6.3.2) * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 8) * Carfilzomib: 56 mg/m2 I.V on days on days 1, 8 and 15 (cycles 7 to 8) * Lenalidomide: 25 mg per day orally from days 1 to 21 * Dexamethasone: 40 mg orally on days 1, 8, 15, 22 (cycles 7 to 8) |
| MRD High-risk patients (post induction MRD >10-5, MRD HR) (1:1 Randomization): Arm C | EXPERIMENTAL | Arm C: ASCT followed by 2 cycles of Isa-KRD (cycles 7 and 8; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone; 28-day cycle) Melphalan 200 mg/m2 followed by autologous stem cell transplantation. * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 8) * Carfilzomib: 56 mg/m2 I.V on days on days 1, 8 and 15 (cycle 7 to 8) * Lenalidomide: 25 mg per day orally from day 1 to day 21 * Dexamethasone: 40 mg orally on days 1, 8, 15, 22 (cycle 7 to 8) |
| MRD High-risk patients (post induction MRD >10-5, MRD HR) (1:1 Randomization): Arm D | EXPERIMENTAL | Tandem ASCT Melphalan 200 mg/m2 followed by autologous stem cell transplantation. |
| Isatuximab/Lenalidomide/Dexamethasone/Bortezomib | EXPERIMENTAL | - |
| Isatuximab/Lenalidomide/Dexamethasone | ACTIVE_COMPARATOR | - |
| Combination Treatment | EXPERIMENTAL | Isatuximab |
| Single Arm | EXPERIMENTAL | Subjects with relapsed or refractory multiple myeloma receiving the study treatment. |
| isatuximab plus lenalidomide after an autologous stem cell transplantation (ASCT) | EXPERIMENTAL | Both isatuximab and lenalidomide are FDA approved and commercially available for the treatment of relapsed or refractory MM (MM that has come back or stopped responding to treatment). Participants will begin taking the study drugs about 60-180 days after your ASCT. Participants may receive the study drugs for about 3 years. After that, participants will have follow-up visits 1 time a year for the 3 years after your last dose of study drugs |
| Isa-RVD | EXPERIMENTAL | Isatuximab (IV): 10 mg/kg on Days 1, 8, 15, 22, 29 in Cycle 1; from Cycle 2 onwards, it will be given on Days 1, 15, 29. Bortezomib (SQ): 1.3 mg/m² on Days 1, 4, 8, 11, 22, 25, 29, and 32. Lenalidomide (PO): 25 mg/day (10 mg/day for patients with creatinine clearance \[CrCl\] ≥30 to \<60 mL/min) from Day 1 to Day 14 and from Day 22 to Day 35 of each cycle. Dexamethasone (IV on the days of Isatuximab and PO on other days): 20 mg/day on Days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23, 25, 26, 29, 30, 32, and 33. If patients are ≥75 years old, dexamethasone will be administered on Days 1, 4, 8, 11, 15, 16, 22, 25, 29 and 32. |
| Induction | EXPERIMENTAL | All participants will receive 4 cycles of induction therapy. Based on the recommendation of investigators, participants may or may not proceed to an autologous stem cell transplant (SCT) after cycles 1-4. Each cycle is 28 days in length (see dosing details below.) For patient undergoing upfront stem cell transplant (SCT): 4 cycles followed by stem cell collection, high-dose chemotherapy, and autologous SCT followed by 2 cycles (called consolidation). For patients deferring SCT following collection: 4 cycles followed by stem cell collection followed by 4 additional cycles. Carfilzomib: 56 mg/m2 IV on days 1, 8,15 Lenalidomide 25 mg orally (PO) on Days 1-21 Isatuximab: 10 mg/kg IV weekly for cycles 1-2 (days 1, 8, 15, 22), then every 2 weeks for cycles 3-6 (days 1 and 15), and monthly (day 1) thereafter Dexamethasone: 20 mg orally (PO) administered day of and day after carfilzomib and isatuximab (days 1, 2, 8, 9, 15, and 16; days 22 and 23 during cycles 1-2 only). |
| Maintenance-High Risk | EXPERIMENTAL | Only patients that have achieved a partial response (PR) or better after induction therapy with or without stem cell transplant will continue on to maintenance therapy. The treatment participants will receive for maintenance will be based on the biological features (or cytogenetics) of participants myeloma and categorized into two groups: Standard-risk and High Risk. High Risk: subjects with high risk cytogenetics (deletion (del 17, translocation (t)(4:14), t(14;16), t(14;20), 1q duplications) will receive the following study treatment for up to two years (24 28-day cycles) until progressive disease (PD) or unacceptable toxicity: Lenalidomide 10 mg orally (PO) Day 1-21 Carfilzomib 56 mg/m2 or last tolerated dose IV Days 1, 15 Isatuximab 10 mg/kg IV Day 1 |
| Maintenance- Standard Risk | EXPERIMENTAL | Only patients that have achieved a partial response (PR) or better after induction therapy with or without stem cell transplant will continue on to maintenance therapy. The treatment participants will receive for maintenance will be based on the biological features (or cytogenetics) of participants myeloma and categorized into two groups: Standard-risk and High Risk. Standard Risk: subjects without high risk cytogenetics (deletion (del 17, translocation (t)(4:14), t(14;16), t(14;20), 1q duplications) will receive the following study treatment for up to two years (24 28-day cycles) until progressive disease (PD) or unacceptable toxicity: \- Lenalidomide 10 mg orally (PO) Day 1-21 |
| Arm I (20 mg dexamethasone, isatuximab, carfilzomib) | EXPERIMENTAL | 20 mg dexamethasone IV given on days 1, 8, 15, 22 (pre- SAR650984 and carfilzomib), then dexamethasone 4 IV or PO mg Day 2, 9, 16. All patients will receive a fixed dose of Isatuximab (SAR650984) according to their assigned dose cohort. Patients receive isatuximab IV over 4-6 hours on days 1 and 15 of every cycle for the starting cohort, and days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Carfilzomib IV will be administered over 10 minutes on days 1, 2, 8, 9, 15, and 16 . Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 courses if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 after 8 cycles per investigator discretion). |
| Arm II (40 mg dexamethasone, isatuximab, carfilzomib) | EXPERIMENTAL | 40 mg dexamethasone IV given on Days 1, 8, 15 and 22 (use as premed to isatuximab). All patients will receive a fixed dose of Isatuximab (SAR650984) according to the assigned dose. Patients receive isatuximab IV over 4-6 hours on day 1, 3-4 hours on Day 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycle (patients may be eligible for rapid siatuximab given over 75 minutes), and carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| Isatuximab | DRUG | Supplied by Sanofi-Aventis (Sanofi); used in induction and maintenance/consolidation strategies in this protocol; administered subcutaneously in the maintenance tables provided; not administered in Arm C. |
| Iberdomide | DRUG | Supplied by Bristol Myers Squibb/Celgene (BMS); used across induction and maintenance phases; administered orally. |
| Bortezomib (B) | DRUG | Commercial supply; used in induction and Arm G maintenance; administered subcutaneously in Arm G on Days 1 and 15 of each 28-day cycle. |
| Dexamethasone | DRUG | Commercial supply; used in induction; may be administered intravenously or orally at investigator discretion; excluded from Arm G. |
| Melphalan | DRUG | Commercial supply; used as conditioning therapy for Arm E before PBSC infusion/ASCT; administered intravenously. |
| Linvoseltamab | DRUG | Supplied by Regeneron; used in Arm F consolidation for 8 cycles before maintenance therapy. |
| On Body Delivery System (OBDS) | DEVICE | Device: On Body Delivery System (OBDS) - Sanofi-Aventis device used with isatuximab administration; abdominal/periumbilical single-site application with post-dose needle retraction and lock-out. |
| Lenalidomide | DRUG | Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3 |
| Bortezomib | DRUG | Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles |
| ASCT | PROCEDURE | ASCT for ams B, C and D during consolidation |
| Pomalidomide | DRUG | Pharmaceutical form: Pill for oral use. Route of administration: 3 mg Pomalidomide 3 mg pill will be taken by mouth once daily on days 1-21 of each 28-day cycle. |
| Dexamethasone (IV) | DRUG | Dexamethasone (IV on the days of Isatuximab and PO on other days): 20 mg/day on Days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23, 25, 26, 29, 30, 32, and 33. If patients are ≥75 years old, dexamethasone will be administered on Days 1, 4, 8, 11, 15, 16, 22, 25, 29 and 32. |
| Bortezomib Injection | DRUG | SQ Oral, predetermined dosage and predetermined days during each cycle |
| Carfilzomib | DRUG | * Induction: protocol determine dose,via IV on 3 days per cycle up to 8 cycles, dependent on Upfront Stem Transplant or Deferring Stem Cell Transplant determination * Maintenance: protocol determine dose,via IV on 2 days per cycle- Maintenance Cycle until progressive disease (PD) or unacceptable toxicity |
Inclusion Criteria: * N- NDMM based on IMWG criteria with clonal bone marrow plasma cells ≥10% or biopsy proven bony or extramedullary disease/plasmacytoma (EMD) with any one or more CRAB-features or myeloma defining events (Rajkumar, 2024) (See Appendix E) * \- Age 18 - 75 years. (Patients aged 71...