Table 3.
Ongoing clinical trials including MRD status in patients' enrollment and/or MRD-driven interventions.
| Identifier | Phase | Regimen/Purpose | Subjects | MRD-driven decision | Primary endpoint | Status |
|---|---|---|---|---|---|---|
| NCT04108624 (MRD2STOP) | PO | Maintenance cessation | 56 multimodality£MRDneg MM patients on a single-agent maintenance for ≥1year | Maintenance cessation | MRD conversion rate, PFS, OS | Not yet recruiting |
| NCT04221178 | PO | Maintenance cessation | 50 MRDneg MM patients for ≥3 years while on continuous maintenance | Maintenance cessation | MRD negativity rate (10−5) a year after enrolling | Recruiting |
| NCT03490344 | 2 | Daratumumab effect on MRDpos patients post induction | 25 MRDpos patients post induction with without consolidative HDT/ASCT | - | MRD negativity rate by MFC | Recruiting |
|
NCT03992170 (DAR4MM) |
2 | Daratumumab effect on MRDpos patients | 50 MRDpos patients with ≥VGPR after any previous therapy | All patients will receive Dara for 24 weeks MRDneg (NGF): treatment cessation MRDpos: Daratumumab every 4 weeks for 80 more weeks |
MRD negativity rate | Recruiting |
|
NCT03901963 (AURIGA) |
3 | DaraR vs. R alone as maintenance treatment | 214 MRDpos (≥10−5)patients post ASCT | - | MRD conversion rate tested by NGS (10−5) | Recruiting |
|
NCT03697655 (PREDATOR) |
2 |
Preventive role of Daratumumab (Dara vs. no intervention) in reappearance of MRD |
274 MRDneg patients after one or two prior lines of therapy | - | EFS | Recruiting |
| NCT02389517 | 2 | Ixa-Rd vs. R alone as maintenance therapy | 86 MRDpos patients after ASCT | - | MRD negativity rate by MFC |
Recruiting |
| NCT02969837 | 2 | Elo-KRd as initial therapy | 55 NDMM non-transplant or transplant eligible agreed to defer ASCT | All with receive Elo-KRD for 12 cycles and then: MRDneg: Elo-Rd maintenance until PD MRDpos: Elo-KRd for 6 more cycles and then Elo-Rd maintenance until PD |
sCR rate, MRD negativity rate by NGS (clonoSIGHT) | Recruiting |
|
NCT04071457 (DRAMMATIC) |
3 | DARArHuPH20 + R vs. R alone as maintenance therapyto direct therapy duration | 1100 patients post ASCT | After 2 years of maintenance with each arm:MRDpos >10−6: Continue with assigned treatment MRDneg (≤ 10−6): Randomization to either stop or continue assigned treatment for up to 7 years |
OS | Recruiting |
| NCT02659293 | 3 | KRd vs. R alone after ASCT | 180 post ASCT that received a maximum of 2 induction regimens and have ≥SD at d100 post ASCT | Carfilzomib cycles 5–8 for MRD- patients that have no risk factors at the end of cycle 6Carfilzomib: cycles 5 - 36 for MRDpos patients with high risk factors at the end of cycle 6 | PFS | Recruiting |
| NCT04096066 | 3 | KRd vs. Rd alone | 340 elderly NDMM not eligible for ASCT | Patients with ≥VGPR & MRDneg (10−5) for ≥ 1 year in the KRD arm will stop K (after ≥ 2 years of treatment) and continue with RD until PD or intolerance | MRD negativity rate, PFS | Recruiting |
| NCT04140162 | 2 | DaraRd induction ± DaraVRd consolidation + DaraR maintenance | 50 NDMM eligible and not for ASCT | Only those with MRD positive status after 6 cycles of induction will receive consolidation | MRD negativity rate after induction and/or consolidation | Not yet recruiting |
| NCT03710603 (PERSEUS) | 3 | DaraVRd arm: DaraVRd for induction and consolidation, DaraR for maintenance VRd arm: VRd for induction and consolidation, R for maintenance |
690 NDMM eligible for ASCT | Patients in DaraVRd group with sustained MRD negativity (10−5) for 12 months and minimum 24 months of maintenance will stop Dara until PD or intolerance Upon recurrence of MRD or loss of CR, patients will restart Dara until PD or intolerance |
PFS | Recruiting |
|
NCT03224507 (MASTER) |
2 | DaraKRd for induction, ASCT ± DaraKRd consolidation ± R maintenance |
82 NDMM eligible for ASCT | MRD (10−5) is evaluated post induction, post ASCT and during each 4-cycle block of Dara-KRd consolidation MRDneg patients after two consecutive evaluations will stop therapy and will be monitored for MRD resurgence (In 6 and 18 months. MRDpos patients post ASCT will complete all cycles of consolidation and if MRD persists, they will receive R maintenance until PD or intolerance |
MRD negativity rate by NGS (clonoSEQ) | Recruiting |
Dara, Daratumumab; d, Dexamethazone; Elo, Elotuzumab; Ixa, Ixazomib; K, Carfilzomib; R, Lenalidomide; V, Velcade; MM, Multiple Myeloma; NDMM, Newly-diagnosed MM; ASCT, Autologous stem-cell transplantation; MRD, Minimal residual disease; NGS, Next-generation sequencing; NGF, Next-generation flow cytometry; MFC, Multicolor flow cytometry; sCR, Stringent complete response; EFS, Event-free survival; PFS, Progression free survival; OS, Overall survival; PO, Prospective observational.
£
Multimodality MRD negativity, MRD negativity by PET/CT and flow cytometry or NGS.