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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
176
Second line treatment will start at MRD reapperance
Second line treatment will start at progressive disease
Ålesund Hospital
Ålesund, Norway
RECRUITINGHaukeland University Hospital
Bergen, Norway
RECRUITINGNordland Hospital Bodø
Bodø, Norway
RECRUITINGSykehuset Ostfold
Fredrikstad, Norway
RECRUITINGFørde Central Hospital
Førde, Norway
RECRUITINGSørlandet Hospital Kristiansand
Kristiansand, Norway
RECRUITINGLevanger Hospital
Levanger, Norway
RECRUITINGAkershus University Hospital
Lørenskog, Norway
RECRUITINGOslo University Hospital
Oslo, Norway
RECRUITINGHelse Stavanger HF
Stavanger, Norway
RECRUITING...and 3 more locations
Progression Free Survival (PFS)
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.
Time frame: 10 years
Overall survival (OS)
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.
Time frame: 11 years
Minimal residual disease negativity after first line treatment
The number of participants who achieve MRD negativity measured by Euroflow NGF at 30-45 after consolidation therapy has ended
Time frame: 30-45 days post consolidation
Time-to-next treatment
Time from end of first line treatment to start of 3.L therapy
Time frame: 10 years
Minimal residual disease negativity during 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).
Time frame: 6 months after starting second line treatment
Health-related quality of life (HRQOL)
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 frame: 10 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.