Back to resultsThe Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study
Primary Purpose
Multiple Myeloma
Status
Recruiting
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Early treatment of relapse with carfilzomib, dexamethasone, daratumumab
Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria part one:
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.
- 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).
Inclusion Criteria part two:
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
Exclusion Criteria part one:
- 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.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
Exclusion Criteria part two:
- 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
Sites / Locations
- Haukeland University HospitalRecruiting
- Nordland Hospital BodøRecruiting
- Sykehuset OstfoldRecruiting
- Førde Central HospitalRecruiting
- Sørlandet Hospital KristiansandRecruiting
- Levanger HospitalRecruiting
- Akershus University HospitalRecruiting
- Oslo University HospitalRecruiting
- Helse Stavanger HFRecruiting
- University Hospital North NorwayRecruiting
- St. Olavs HospitalRecruiting
- The Hospital of VestfoldRecruiting
- Ålesund HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm Description
Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response.
Patients will be followed up by standard criteria and start 2.L treatment at progressive disease.
Outcomes
Primary Outcome Measures
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.
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.
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
Secondary Outcome Measures
Time-to-next treatment
Time from end of first line treatment to start of 3.L therapy
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).
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.
Full Information
NCT ID
NCT04513639
First Posted
August 12, 2020
Last Updated
September 20, 2022
Sponsor
Oslo University Hospital
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
1. Study Identification
Unique Protocol Identification Number
NCT04513639
Brief Title
The Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study
Official Title
The Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 27, 2020 (Actual)
Primary Completion Date
June 1, 2031 (Anticipated)
Study Completion Date
June 1, 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
176 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response.
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Patients will be followed up by standard criteria and start 2.L treatment at progressive disease.
Intervention Type
Drug
Intervention Name(s)
Early treatment of relapse with carfilzomib, dexamethasone, daratumumab
Other Intervention Name(s)
DKd
Intervention Description
Second line treatment will start at MRD reapperance
Intervention Type
Drug
Intervention Name(s)
Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab
Other Intervention Name(s)
DKd
Intervention Description
Second line treatment will start at progressive disease
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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
Title
Overall survival (OS)
Description
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
Title
Minimal residual disease negativity after first line treatment
Description
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
Secondary Outcome Measure Information:
Title
Time-to-next treatment
Description
Time from end of first line treatment to start of 3.L therapy
Time Frame
10 years
Title
Minimal residual disease negativity during second line treatment
Description
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
Title
Health-related quality of life (HRQOL)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria part one:
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.
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).
Inclusion Criteria part two:
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
Exclusion Criteria part one:
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.
Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
Exclusion Criteria part two:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anne-Marie Rasmussen, PhD
Phone
+4799791064
Email
annemra55@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Lysen, MSC
Phone
+4747246569
Email
annaly@ous-hf.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fredrik Schjesvold, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Galina Tsykonova, MD
Email
tor.henrik.anderson.tvedt@helse-bergen.no
Facility Name
Nordland Hospital Bodø
City
Bodø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Randi F Halstensen, MD
Phone
+4775534000
Email
randi.fykse.hallstensen@nordlandssykehuset.no
Facility Name
Sykehuset Ostfold
City
Fredrikstad
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birgitte D. Eiken, MD
Email
birgitte.dahl.eiken@so-hf.no
Facility Name
Førde Central Hospital
City
Førde
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damian Szatkowski, MD
Phone
+4757839000
Email
damian.szatkowski@helse-forde.no
Facility Name
Sørlandet Hospital Kristiansand
City
Kristiansand
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jurgen Rolke, MD
Phone
+4790610600
Email
jurgen.rolke@sshf.no
Facility Name
Levanger Hospital
City
Levanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon Hjalmar Sørbø, MD
Phone
+4774098000
Email
jonhjalmar.sorbo@helse-nordtrondelag.no
Facility Name
Akershus University Hospital
City
Lørenskog
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anette L. Eilertsen, MD, PhD.
Email
anette.loken.eilertsen@ahus.no
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fredrik Schjesvold, MD, PhD
Email
fredrikschjesvold@gmail.com
First Name & Middle Initial & Last Name & Degree
Frida Askeland, MD
Email
friask@ous-hf.no
Facility Name
Helse Stavanger HF
City
Stavanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Einar Haukås, MD, PhD
Email
einar.haukas@sus.no
Facility Name
University Hospital North Norway
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anders Vik, MD, PhD
Email
Anders.Vik@unn.no
Facility Name
St. Olavs Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Slørdahl, MD, PhD
Email
Tobias.Schmidt.Slordahl@stolav.no
Facility Name
The Hospital of Vestfold
City
Tønsberg
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Magnus Moksnes, MD
Email
magmok@siv.no
Facility Name
Ålesund Hospital
City
Ålesund
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Brudevold, MD
Phone
+4740622848
Email
robert.brudevold@helse-mr.no
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study
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