Title
MRD-Guided Sequential Therapy For Deep Response in Newly Diagnosed Multiple Myeloma - MASTER-2 (MM 160) Trial

Description
This research study will determine the proportion of patients with lowest minimal residual disease (MRD) response obtainable after receiving 6 cycles of study treatment. Minimal residual disease is multiple myeloma cells below the level of 1 cancer cell out of 100,000 in the bone marrow.

For patients who become MRD "negative" (i.e. less than 1 cancer cell out of 100,000) at the end of 6 cycles of therapy, this study will study if that good response can be maintained with 3 additional cycles of treatment instead of use of autologous hematopoietic cell transplantation (AHCT).

For patients who are MRD "positive" at the end of 6 cycles of therapy, this study will answer whether more patients can become and remain MRD "negative" with AHCT plus teclistamab in combination with daratumumab when compared with patients who undergo AHCT followed by lenalidomide (an established anti-myeloma drug) plus daratumumab.

Objective
PRIMARY OBJECTIVE:
- All patients: To describe the depth of response obtainable with 6 cycles of quadruplet therapy with daratumumab, bortezomib, lenalidomide and dexamethasone in patients with NDMM.
- MRD Negative Cohort (patients MRD negative at end of induction): To assess whether in patients with NDMM and MRD negativity at end of induction, AHCT can be safely deferred without compromise in disease control.
- MRD Positive Cohort (patients with MRD positive at the end of induction): To assess whether in patients with NDMM and MRD positive at end of induction, intensification and maintenance with the BCMA-CD3 T-cell engager Teclistamab in combination
with daratumumab following AHCT will increase likelihood of achieving and sustaining MRD negativity (MRD<10-5) when compared to AHCT followed by Lenalidomide and daratumumab intensification/maintenance.

SECONDAY OBJECTIVES AND ENDPOINTS:
- MRD negative and MRD positive cohorts: PFS in Arms A vs. B and in arms C vs. D, OS in arms A vs. B and in arms C vs. D
- MRD positive cohort: to compare the rate of conversion of MRD from >/= 10-5 (MRD1x) to < 10-5 after consolidation with Tec-Dara in arm C or Dara-R in arm D
- MRD positive patients randomized to arm C: to determine the safety of Tec-Dara when administered as post AHCT consolidation and maintenance
- All patients reaching MRD-SURE: to compare the long-term kinetics of MRD resurgence between arms A and B and between arms C and D

Treatment Drug: Dara-VRd intensification, Dara-R maintenance
Drug: AHCT intensification, Dara-R maintenance
Drug: AHCT intensification, Tec-Dara consolidation, Tec-Dara maintenance
Drug: AHCT intensification, Dara-R consolidation, Dara-R maintenance
Drug: Dara-VRd induction

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital