The Relapse from MRD Negativity As Indication for Treatment (REMNANT) Study

Phase 2

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab; Drug: Early treatment of relapse with carfilzomib, dexamethasone, daratumumab

• Registration Number: NCT04513639
• Lead Sponsor: Oslo University Hospital

Brief Summary

The REMNANT study will evaluate whether treating minimal residual disease (MRD) relapse after first line treatment prolongs progression free survival and overall survival for myeloma patients versus treating relapse after first line treatment at progressive disease. To establish a homogenous group of MRD negative patients after first line treatment including autologous stem cell transplantation, patients are enrolled at diagnosis and treated with Norwegian standard of care first line treatment. MRD negative patients will move on to the randomized part.

Detailed Description

391 patients with newly diagnosed multiple myeloma eligible for high dose therapy with autologous stem cell support will be included in the phase II part of the study and receive standard of care first line treatment according to Norwegian national guidelines; bortezomib- lenalidomide - dexamethasone for 4 pre-transplant induction and 4 post-transplant consolidation cycles (all 21-d cycles). After induction patients will undergo tandem or single ASCT, depending on toxicity and response to first ASCT. The primary endpoint of the phase 2 part of the study is the number of patients who achieve MRD negative (Euroflow NGF 10 -5 ) complete response 30-45 days post consolidation. Patients (176) achieving MRD negative complete response will be randomly assigned in a 1:1 ratio to receive second line treatment at MRD reappearance (arm A) or at progressive disease as defined by the IMWG criteria (arm B). Randomization will be stratified by R-ISS stage at diagnosis and single vs tandem ASCT. Patients in arm A will be followed with MRD assessment every 4 month and start second line treatment at loss of MRD negative CR. Patients in arm B will be followed up by standard criteria and start second line treatment at progressive disease. Both arms will receive the same 2.L treatment; carfilzomib - dexamethasone - daratumumab. (all 28-d cycles) Second line treatment will continue until disease progression, unacceptable AEs or patient withdrawal. In arm A MRD Euroflow will be assessed after 6 and 18 months of 2L therapy. In arm B MRD Euroflow will be assessed if \>CR is achieved but not before 6 months of 2 L therapy, and again after 12 consecutive months.

Study Timeline

• Study First Submitted: 2020-08-12
• Study First Submitted QC: 2020-08-12
• Study First Posted: 2020-08-14
• Study Start: 2020-08-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-20
• Primary Completion: 2031-06-01
• Study Completion: 2032-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 176

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab	Patients will be followed up by standard criteria and start 2.L treatment at progressive disease.
Arm A	Early treatment of relapse with carfilzomib, dexamethasone, daratumumab	Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	10 years	Median PFS of Arm A (MRD guided) vs Arm B (PD guided) defined as the time from randomization to disease progression or death due to any cause following 2.L treatment.
Minimal residual disease negativity after first line treatment	30-45 days post consolidation	The number of participants who achieve MRD negativity measured by Euroflow NGF at 30-45 after consolidation therapy has ended
Overall survival (OS)	11 years	Median OS of Arm A vs Arm B (MRD guided) defined as the time from randomization to death of any cause following 2.L treatment.

Secondary Outcome Measures

Name	Time	Method
Minimal residual disease negativity during second line treatment	6 months after starting second line treatment	The proportion of patients who achieve MRD negativity during 2.L treatment, monitored by MRD Euroflow NGF at 6 and 18 months in arm A and after achieving CR in arm B (first MRD testing after 6 months).
Health-related quality of life (HRQOL)	10 years	Patient reported outcome HRQOL forms will be filled out by patients at defined time points during the study and finally at relapse after 2.L therapy.
Time-to-next treatment	10 years	Time from end of first line treatment to start of 3.L therapy

Trial Locations

Locations (13)

Førde Central Hospital; 🇳🇴 Førde, Norway

Haukeland University Hospital; 🇳🇴 Bergen, Norway

Nordland Hospital Bodø; 🇳🇴 Bodø, Norway

Sykehuset Ostfold; 🇳🇴 Fredrikstad, Norway

Sørlandet Hospital Kristiansand; 🇳🇴 Kristiansand, Norway

Akershus University Hospital; 🇳🇴 Lørenskog, Norway

Levanger Hospital; 🇳🇴 Levanger, Norway

Helse Stavanger HF; 🇳🇴 Stavanger, Norway

University Hospital North Norway; 🇳🇴 Tromsø, Norway

Oslo University Hospital; 🇳🇴 Oslo, Norway

Ålesund Hospital; 🇳🇴 Ålesund, Norway

St. Olavs Hospital; 🇳🇴 Trondheim, Norway

The Hospital of Vestfold; 🇳🇴 Tønsberg, Norway