Multiple MyelomaPhase 2/3NCT04513639
The Relapse from MRD Negativity As Indication for Treatment (REMNANT) Study
A Phase 2/3 study testing Early treatment of relapse with carfilzomib, dexamethasone, daratumumab and Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab in people with Multiple Myeloma, run by Oslo University Hospital at 13 sites in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Early treatment of relapse with carfilzomib, dexamethasone, daratumumab and Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 13 sitesNorway
- Study dates
- 27 Aug 2020to 1 Jun 2032
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Patient with newly diagnosed multiple myeloma (IMWG criteria) eligible for high-dose therapy and ASCT.
- Patient must be >18 and < 75 years of age at the time of signing the informed consent
- Must have measurable disease as defined by the International Myeloma Working Group; serum monoclonal paraprotein (M-protein) level > 10 g/L or light chain multiple myeloma without measurable disease in the serum; serum immunoglobulin FLC > 100 mg/L and abnormal serum immunoglobulin kappa lambda FLC ratio.
- Voluntary written informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. ECOG 3 can be enrolled if caused by myeloma.
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- Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements.
- Female of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test within 7 days prior to inclusion.
- FCBP and male subject who are sexually active with FCBP must agree to use highly effective concomitant methods of contraceptive during the study and for at least 28 days following the last study drug dose. Male subjects must use contraception and refrain from donating sperm for at least 28 days after the last dose of lenalidomide according to Pregnancy Prevention Plan (Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information).
- Each patient must meet all of the following inclusion criteria to be enrolled in the study
- Patient must be MRD negative measured by Euroflow NGF after 1.L therapy. The cutoff for inclusion into part 2 will be 100 PC per 10 mill. nucleated cells monitored in BM.
- Has received 1.L treatment in part 1 of the study.
- ECOG performance status score 0, 1 or 2
Who cannot join
- Received more than one cycle of induction treatment for multiple myeloma.
- Patient with ongoing or active systemic infection, active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive
- Concurrent medical or psychiatric condition or disease that is incompatible to HDM and ASCT or that will likely result in reduced study compliance and reduce ability to follow study procedures, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
- No active malignancy with a lower life expectancy than myeloma
- Female patient who have a positive serum pregnancy test during the screening period.
- Female patient who is lactating during the screening period but are not willing to stop lactating prior to the first treatment cycle starts.
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- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- No active malignancy with a lower life expectancy than myeloma
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Norway13 sites, 13 recruiting
- Recruiting
Ålesund Hospital
Ålesund
Robert Brudevold, MD, +4740622848, robert.brudevold@helse-mr.no
- Recruiting
Haukeland University Hospital
Bergen
Galina Tsykonova, MD, tor.henrik.anderson.tvedt@helse-bergen.no
- Recruiting
Nordland Hospital Bodø
Bodø
Randi F Halstensen, MD, +4775534000, randi.fykse.hallstensen@nordlandssykehuset.no
- Recruiting
Førde Central Hospital
Førde
Damian Szatkowski, MD, +4757839000, damian.szatkowski@helse-forde.no
- Recruiting
Sykehuset Ostfold
Fredrikstad
Birgitte D. Eiken, MD, birgitte.dahl.eiken@so-hf.no
- Recruiting
Sørlandet Hospital Kristiansand
Kristiansand
Jurgen Rolke, MD, +4790610600, jurgen.rolke@sshf.no
- Recruiting
Levanger Hospital
Levanger
Jon Hjalmar Sørbø, MD, +4774098000, jonhjalmar.sorbo@helse-nordtrondelag.no
- Recruiting
Akershus University Hospital
Lørenskog
Anette L. Eilertsen, MD, PhD., anette.loken.eilertsen@ahus.no
- Recruiting
Oslo University Hospital
Oslo
Fredrik Schjesvold, MD, PhD, fredrikschjesvold@gmail.com
Frida Askeland, MD, friask@ous-hf.no
- Recruiting
Helse Stavanger HF
Stavanger
Einar Haukås, MD, PhD, einar.haukas@sus.no
- Recruiting
The Hospital of Vestfold
Tønsberg
Magnus Moksnes, MD, magmok@siv.no
- Recruiting
University Hospital North Norway
Tromsø
Anders Vik, MD, PhD, Anders.Vik@unn.no
- Recruiting
St. Olavs Hospital
Trondheim
Tobias Slørdahl, MD, PhD, Tobias.Schmidt.Slordahl@stolav.no
About this study
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Early treatment of relapse with carfilzomib, dexamethasone, daratumumab, Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early treatment of relapse with carfilzomib, dexamethasone, daratumumabDrug
Also called DKd
Second line treatment will start at MRD reapperance
Standard treatment of relapse with carfilzomib, dexamethasone, daratumumabDrug
Also called DKd
Second line treatment will start at progressive disease
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response. Receives: Drug: Early treatment of relapse with carfilzomib, dexamethasone, daratumumab |
| Arm B | Active comparator | Patients will be followed up by standard criteria and start 2.L treatment at progressive disease. Receives: Drug: Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 30-45 days post consolidation
Secondary outcomes (3)
Time-to-next treatment
Time from end of first line treatment to start of 3.L therapy
Measured: 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).
Measured: 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.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2020
- Study start27 Aug 2020
- Primary completion1 Jun 2031 (estimated)
- Study completion1 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 176 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- St. Olavs Hospital, Haukeland University Hospital, University Hospital of North Norway, University Hospital, Akershus, Helse Stavanger HF, Førde Central Hospital, Sorlandet Hospital HF, Nordlandssykehuset HF, The Hospital of Vestfold, Helse Nord-Trøndelag HF, Alesund Hospital, Sykehuset Ostfold
- Responsible party
- Principal investigator, Fredrik Hellem Schjesvold, Oslo University Hospital
- Investigators
- Fredrik Schjesvold, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04513639
- Sponsor's protocol ID
- OMC01/19
- Status last verified
- Mar 2025
- First submitted
- 12 Aug 2020
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Askeland FB, Bugge VH, Rasmussen AM, Lysen A, Haukas E, Moksnes M, Eilertsen AL, Tsykunova G, Eiken BD, Leknes NM, Rolke J, Stavseth V, Samstad E, Hallstensen RF, Szatkowski D, Hansen AA, Nilsen AS, Slordahl TS, Abdollahi P, Schjesvold F. Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma. Blood Cancer J. 2025 Dec 22;15(1):214. doi: 10.1038/s41408-025-01407-5.
PubMed 41429779
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relapse from MRD Negativity As Indication for Treatment (REMNANT) Study
- ClinicalTrials.gov ID
- NCT04513639
- Acronym / sponsor ID
- OMC01/19
- Conditions
- Multiple Myeloma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 176 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- St. Olavs Hospital, Haukeland University Hospital, University Hospital of North Norway, University Hospital, Akershus, Helse Stavanger HF, Førde Central Hospital, Sorlandet Hospital HF, Nordlandssykehuset HF, The Hospital of Vestfold, Helse Nord-Trøndelag HF, Alesund Hospital, Sykehuset Ostfold
- Study start
- 27 Aug 2020 (actual)
- Primary completion
- 1 Jun 2031 (estimated)
- Study completion
- 1 Jun 2032 (estimated)
- First posted
- 14 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Early treatment of relapse with carfilzomib, dexamethasone, daratumumabPatients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response. |
| Arm B | Active comparator | Drug: Standard treatment of relapse with carfilzomib, dexamethasone, daratumumabPatients will be followed up by standard criteria and start 2.L treatment at progressive disease. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Each patient must meet all of the following inclusion criteria to be enrolled in the study
Key exclusion criteria (9 listed)
- Received more than one cycle of induction treatment for multiple myeloma.
- Patient with ongoing or active systemic infection, active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive
- Concurrent medical or psychiatric condition or disease that is incompatible to HDM and ASCT or that will likely result in reduced study compliance and reduce ability to follow study procedures, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
- No active malignancy with a lower life expectancy than myeloma
- Female patient who have a positive serum pregnancy test during the screening period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early treatment of relapse with carfilzomib, dexamethasone, daratumumabAlso: DKdSecond line treatment will start at MRD reapperance | Drug | Arm A |
| Standard treatment of relapse with carfilzomib, dexamethasone, daratumumabAlso: DKdSecond line treatment will start at progressive disease | Drug | Arm B |
Primary outcome
Progression Free Survival (PFS)
Time frame: 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.
Overall survival (OS)
Time frame: 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.
Minimal residual disease negativity after first line treatment
Time frame: 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
3 secondary outcomes
Time-to-next treatment
Time frame: 10 years
Minimal residual disease negativity during second line treatment
Time frame: 6 months after starting second line treatment
Health-related quality of life (HRQOL)
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Derived from this study: PubMed 41429779Askeland FB, Bugge VH, Rasmussen AM, Lysen A, Haukas E, Moksnes M, Eilertsen AL, Tsykunova G, Eiken BD, Leknes NM, Rolke J, Stavseth V, Samstad E, Hallstensen RF, Szatkowski D, Hansen AA, Nilsen AS, Slordahl TS, Abdollahi P, Schjesvold F. Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma. Blood Cancer J. 2025 Dec 22;15(1):214. doi: 10.1038/s41408-025-01407-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fredrik Schjesvold, MD, PhD principal investigator
Oslo University Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Early treatment of relapse with carfilzomib, dexamethasone, daratumumab and Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab in people with Multiple Myeloma, run by Oslo University Hospital at 13 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne-Marie Rasmussen, PhD (+4799791064, annemra55@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: 10 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04513639, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.