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

NCT ID: NCT04513639

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-27
• Study Completion Date: 2032-06-01

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response.

Group Type: EXPERIMENTAL

Early treatment of relapse with carfilzomib, dexamethasone, daratumumab

Intervention Type: DRUG

Second line treatment will start at MRD reapperance

Arm B

Patients will be followed up by standard criteria and start 2.L treatment at progressive disease.

Group Type: ACTIVE_COMPARATOR

Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab

Intervention Type: DRUG

Second line treatment will start at progressive disease

Interventions

Early treatment of relapse with carfilzomib, dexamethasone, daratumumab

Second line treatment will start at MRD reapperance

Intervention Type: DRUG

Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab

Second line treatment will start at progressive disease

Intervention Type: DRUG

Other Intervention Names

DKd; DKd

Eligibility Criteria

Inclusion Criteria

1. Patient with newly diagnosed multiple myeloma (IMWG criteria) eligible for high-dose therapy and ASCT.

2. Patient must be >18 and < 75 years of age at the time of signing the informed consent

3. 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.

4. Voluntary written informed consent

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. ECOG 3 can be enrolled if caused by myeloma.

6. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements.

7. Female of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test within 7 days prior to inclusion.

8. 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).

1. 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.

2. Has received 1.L treatment in part 1 of the study.

3. ECOG performance status score 0, 1 or 2

Exclusion Criteria

1. Received more than one cycle of induction treatment for multiple myeloma.

2. Patient with ongoing or active systemic infection, active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive

3. 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.

4. No active malignancy with a lower life expectancy than myeloma

5. Female patient who have a positive serum pregnancy test during the screening period.

6. Female patient who is lactating during the screening period but are not willing to stop lactating prior to the first treatment cycle starts.

7. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

1. No active malignancy with a lower life expectancy than myeloma

2. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role: collaborator

Førde Central Hospital

OTHER

Sponsor Role: collaborator

Sorlandet Hospital HF

OTHER_GOV

Sponsor Role: collaborator

Nordlandssykehuset HF

OTHER

Sponsor Role: collaborator

The Hospital of Vestfold

OTHER

Sponsor Role: collaborator

Helse Nord-Trøndelag HF

OTHER

Sponsor Role: collaborator

Alesund Hospital

OTHER

Sponsor Role: collaborator

Sykehuset Ostfold

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fredrik Hellem Schjesvold

Head of Oslo Myeloma Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fredrik Schjesvold, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Ålesund Hospital

Ålesund, , Norway

Site Status: RECRUITING

Haukeland University Hospital

Bergen, , Norway

Site Status: RECRUITING

Nordland Hospital Bodø

Bodø, , Norway

Site Status: RECRUITING

Sykehuset Ostfold

Fredrikstad, , Norway

Site Status: RECRUITING

Førde Central Hospital

Førde, , Norway

Site Status: RECRUITING

Sørlandet Hospital Kristiansand

Kristiansand, , Norway

Site Status: RECRUITING

Levanger Hospital

Levanger, , Norway

Site Status: RECRUITING

Akershus University Hospital

Lørenskog, , Norway

Site Status: RECRUITING

Oslo University Hospital

Oslo, , Norway

Site Status: RECRUITING

Helse Stavanger HF

Stavanger, , Norway

Site Status: RECRUITING

University Hospital North Norway

Tromsø, , Norway

Site Status: RECRUITING

St. Olavs Hospital

Trondheim, , Norway

Site Status: RECRUITING

The Hospital of Vestfold

Tønsberg, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Anne-Marie Rasmussen, PhD

Role: CONTACT

annemra55@gmail.com

+4799791064

Anna Lysen, MSC

Role: CONTACT

annaly@ous-hf.no

+4747246569

Facility Contacts

Robert Brudevold, MD

Role: primary

robert.brudevold@helse-mr.no

+4740622848

Galina Tsykonova, MD

Role: primary

tor.henrik.anderson.tvedt@helse-bergen.no

Randi F Halstensen, MD

Role: primary

randi.fykse.hallstensen@nordlandssykehuset.no

+4775534000

Birgitte D. Eiken, MD

Role: primary

birgitte.dahl.eiken@so-hf.no

Damian Szatkowski, MD

Role: primary

damian.szatkowski@helse-forde.no

+4757839000

Jurgen Rolke, MD

Role: primary

jurgen.rolke@sshf.no

+4790610600

Jon Hjalmar Sørbø, MD

Role: primary

jonhjalmar.sorbo@helse-nordtrondelag.no

+4774098000

Anette L. Eilertsen, MD, PhD.

Role: primary

anette.loken.eilertsen@ahus.no

Fredrik Schjesvold, MD, PhD

Role: primary

fredrikschjesvold@gmail.com

Frida Askeland, MD

Role: backup

friask@ous-hf.no

Einar Haukås, MD, PhD

Role: primary

einar.haukas@sus.no

Anders Vik, MD, PhD

Role: primary

Anders.Vik@unn.no

Tobias Slørdahl, MD, PhD

Role: primary

Tobias.Schmidt.Slordahl@stolav.no

Magnus Moksnes, MD

Role: primary

magmok@siv.no

Other Identifiers

OMC01/19

Identifier Type: -

Identifier Source: org_study_id