Table 1.
Phase III clinical trials in myeloma using MRD assessment as primary or secondary endpoints.
| Trial ID | Sponsor | Eligibility | Enrollment | Interventions (Trial name) | MRD-based endpointsa | Publications |
|---|---|---|---|---|---|---|
| NCT03652064 | Janssen Research and Development, LLC | Newly diagnosed multiple myeloma (NDMM) not undergoing hematopoietic stem cell transplant (HSCT) | 395 | Daratumumab, Bortezomib, Lenalidomide, Dexamethasone (CEPHEUS) | MRD negativity [after randomization and prior to progressive disease (PD) or subsequent anti-myeloma therapyb], MRD negative rate (1 year, throughout study) | J Clin Oncol 2019;37(15 Suppl): abstr TPS8056 |
| NCT04071457 | Southwest Oncology Group | Multiple myeloma (MM) patients who have undergone systemic induction therapy and autologous stem cell transplantation (ASCT) | 1,100 | Lenalidomide, Daratumumab/rHuPH20 (DRAMMATIC) | MRD negativity (24 months from initial randomization) | |
| NCT04096066 | Fondazione Neoplasie Sangue Onlus | Patients with NDMM ≥ 65 years | 340 | Carfilzomib, Lenalidomide, Dexamethasone | MRDb, MRD negativity (5 years) | |
| NCT03941860 | NCI | Previously diagnosed patients with MM on lenalidomide maintenance post stem cell transplantation (SCT) | 510 | Ixazomib, Ixazomib Citrate, Lenalidomide (OPTIMUM) | MRD conversion rate (at 12 and 24 cycles post-randomization) | |
| NCT02406144 | PETHEMA Foundation | Patients with NDMM after ASCT | 316 | MLN9708, Lenalidomide, Dexamethasone | MRD (5 years) | |
| NCT03948035 | Wuerzburg University Hospital | Patients with NDMM eligible for ASCT | 576 | Elotuzumab, Carfilzomib, Lenalidomide, ASCT | MRD negativity rate (end of cycle 6b) | |
| NCT03710603 | European Myeloma Network | Patients with NDMM | 690 | Daratumumab, Velcade, Lenalidomide, Dexamethasone (PERSEUS) | Post-consolidation MRD negativity rate | J Clin Oncol 2019;37(15 Suppl): abstr TPS8055 |
| NCT03617731 | U. of Heidelberg Medical Center | Untreated patients with NDMM requiring systemic therapy | 662 | Lenalidomide, Bortezomib, Dexamethasone, Isatuximab (GMMG HD7) | MRD negativity (post inductionb, post therapy, during and after maintenance) | |
| NCT03562169 | U. of Leeds | Relapsed patients with MM previously treated with ASCT | 406 | Ixazomib, thalidomide, & dexamethasone (ITD), Augmented and conventional ASCT (ACCoRd) | MRD negativity rate, continuous MRD (baseline, end of re-induction, 100 days post-ASCT, After two cycles of consolidation; 8 weeks and 12 months post-randomization 2) | |
| NCT03275285 | Sanofi | Relapsed and/or refractory patients with MM previously treated with 1 to 3 lines of therapy | 302 | Isatuximab, SAR650984, carfilzomib, dexamethasone (IKEMA) | MRD negativity (36 months) | J Clin Oncol 2018;36(15 Suppl): abstr TPS8060 |
| NCT03720041 | U. of Leeds | Patients with NDMM non-eligible for SCT | 740 | Ixazomib, Lenalidomide, Dexamethasone (IRD) (FiTNEss) | MRD negativity (end of induction therapy and 12 months post randomization 2) | |
| NCT02659293 | U. of Chicago | Patients with MM after ASCT being considered for lenalidomide maintenance. | 180 | Lenalidomide, Carfilzomib, Dexamethasone | MRD negativity rate (6 and 12 months after randomization) | |
| NCT03319667 | Sanofi | Patients with NDMM not eligible for transplant | 475 | Isatuximab, Bortezomib, Lenalidomide, Dexamethasone (IMROZ) | MRD negativity rate (60 months after the FPI or scheduled assessment) | |
| NCT04091126 | GlaxoSmithKline | Transplant ineligible (TI) newly diagnosed multiple myeloma (NDMM). | 750 | Belantamab mafodotin, Bortezomib, Lenalidomide, Dexamethasone | % of patients with sustained MRD negativity (1 year) | |
| NCT02136134 | Janssen Res. & Dev., LLC | Patients with relapsed or refractory MM (RRMM) | 499 | Daratumumab, Bortezomib and Dexamethasone | MRD negativity rate (up to disease progression) | PMID: 27557302 |
| NCT03158688 | Amgen | Patients with RRMM | 466 | Dexamethasone, Daratumumab, Carfilzomib (CANDOR) | MRD[-]CR (12 and 28 months) | Blood 2019;134 (Suppl 2):LBA-6 |
| NCT02181413 | Millennium Pharmaceuticals, Inc. | Patients with NDMM responsive to induction therapy and who have received high-dose therapy and ASCT | 656 | Ixazomib Citrate | MRD conversion rate, maintenance of MRD negativity [EOT (24 months)] | PMID: 30545780 |
| NCT04181827 | Janssen Res. & Dev., LLC | Patients with relapsed and lenalidomide-refractory MM | 400 | JNJ-68284528, Pomalidomide, Bortezomib, Dexamethasone, Daratumumab (CARTITUDE-4) | MRD negativity rate overall and in participants with CR or sCR, sustained MRD negative rate (6 years) | ASH 2019; abstr 577 |
| NCT01863550 | ECOG-ACRIN Cancer Research Group | Patients with NDMM | 1,087 | Bortezomib, Carfilzomib, Dexamethasone, Lenalidomide | MRD negativity rate [post induction randomization and post-maintenance randomization (2,3 years)] | |
| NCT03748953 | Millennium Pharmaceuticals, Inc. | Patients with NDMM with CR/VGPR/PR to initial therapy and who have not undergone SCT | 105 | Ixazomib | MRD conversion rate (24 months) | |
| NCT03993912 | University Hospital, Lille | Elderly frail patients with NDMM ineligible for high-dose chemotherapy and ASCT | 294 | Daratumumab, Lenalidomide, Dexamethasone (IFM2017_03) | MRD negativity rate (12 months) | |
| NCT02541383 | Intergroupe Francophone du Myelome | Transplant eligible previously untreated patients with MM | 1,085 | Bortezomib, Thalidomide, Dexamethasone, Daratumumab (Cassiopeia) | MRD negativity (post-consolidation, post-ASCT) | PMID: 31171419 |
| NCT04162210 | GlaxoSmithKline | Patients with RRMM | 380 | Belantamab, Pomalidomide plus low-dose Dexamethasone | MRD negativity rate (up to 55 months) | |
| NCT02252172 | Janssen Res. & Dev., LLC | Patients with NDMM not eligible for either high-dose chemotherapy or ASCT. | 737 | Daratumumab, Lenalidomide, Dexamethasone | MRD negativity rate (any timepoint after randomization to 60 months post C1D1 with an expected average of 24 months) | PMID: 31141632 |
| NCT03539744 | AbbVie | t(11;14)-positive patients with RRMM | 244 | Pomalidomide, Dexamethasone, Venetoclax (CANOVA) | MRD negativity rate (28 months from first randomization) | |
| NCT03651128 | Celgene | Patients with RRMM | 381 | bb2121, Daratumumab, Pomalidomide, Dexamethasone, Bortezomib, Ixazomib, Lenalidomide (KarMMa-3) | MRD (5 years from randomization) | |
| NCT03180736 | European Myeloma Network; Collab.: Janssen Res & Dev, LLC | Patients with RRMM | 304 | Daratumumab, Pomalidomide, Dexamethasone | MRD negativity rate [from randomization until PD (approximately up to 3 years)] | J Clin Oncol 2018;36(15 Suppl): abstr 8059 |
| NCT03729804 | University of Chicago | Newly diagnosed untreated patients with MM requiring systemic chemotherapy | 250 | Carfilzomib, Lenalidomide, Dexamethasone, Bortezomib (COBRA) | MRD negativity at indicated timepoints of study after randomization (5 years) | |
| NCT03792620 | Grupo de Estudos Multicentricos em Onco-Hematologia | Newly diagnosed myeloma in older patients (≤65 years) without comorbidity | 20 | Cyclo Thal Dex Daratumumab (MAXDARA) | MRD negativity rate (24 months) | |
| NCT02312258 | Millennium Pharmaceuticals, Inc. | Patients with NDMM with CR, VGPR, or PR to initial therapy and who have not undergone SCT | 706 | Ixazomib (TOURMALINE-MM4) | MRD conversion rate, maintenance of MRD negativity (screening, cycle 13, and cycle 26) | TOURMALINE-MM4_Mmhub.com |
| NCT02076009 | Janssen Res. & Dev., LLC | Patients with RRMM | 569 | Daratumumab, Lenalidomide, Dexamethasone (POLLUX) | MRD negativity rate from randomization to the date of first documented evidence of PD until 3 years | J Clin Oncol 2017;35(15 Suppl): abstr 8025 |
| NCT02990338 | Sanofi | Patients with RRMM | 307 | Isatuximab, Pomalidomide, Dexamethasone (ICARIA-MM) | Number of participants with MRD (up to 76.7 weeks) | PMID: 31735560 |
| NCT02195479 | Janssen Res. & Dev., LLC | Untreated patients with MM ineligible for high-dose chemotherapy and ASCT | 706 | Velcade, Melphalan, Prednisone, Daratumumab, Dexamethasone | Percentage of participants with negative MRD [from randomization to disease progression (up to 2.4 years)] | PMID: 29231133 |
| NCT03859427 | Amgen | Patients with RRMM | 460 | Carfilzomib, Lenalidomide, Dexamethasone (ARROW2) | MRD[-]CR rate (time frame: 12 months and study completion) | Clin Lymphoma Myeloma Leuk 2019;19(Suppl 1):S332-S333 |
| NCT03901963 | Janssen Res. & Dev., LLC | Patients with NDMM who have undergone four to eight cycles of induction and/or consolidation, HDT and ASCT | 214 | Daratumumab, Lenalidomide (AURIGA) | MRD negativity rate (12b, 36 months) |
aSecondary endpoint unless otherwise noted.
bPrimary endpoint.