RElapse from Mrd Negativity As iNdication for Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Immune System Diseases [C20]

Trial duration

26 Sep 2024 → ongoing

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GSK · Janssen/J&J Innovative Medicine · Norwegian Cancer society · The Binding Site · The Norwegian Government · BMS

External identifiers

EU CT number

2023-510215-18-00

EudraCT number

2019-004401-27

ClinicalTrials.gov

NCT04513639

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Phase II/Part1: To determine how many patients who achieve MRD negativity after standard induction, transplant and consolidation therapy
Phase III/Part 2: The primary objective 1 is to determine whether starting treatment at first sign of malignant plasma cells in the bone marrow measured by MRD (early treatment group) prolongs progression-free survival (PFS) compared with standard indication for relapse treatment according to IMWG guidelines.

Secondary objectives 2

1. Part 1. To determine the Progression Free Survival (PFS) rate after 4 cycles of VRd consolidation treatment 2. To determine the Overall Survival (OS) rate after 4 cycles of VRd consolidation treatment 3. To assess the safety profile of first line treatment when including VRd as a consolidation step 4. To assess ORR after 4 cycles of VRd consolidation treatment
2. Part 2: To determine the time from randomization to start of 3.L therapy (TTNT) 2. To determine the rate of MRD negativity during 2.L treatment, 3. To evaluate how starting treatment early vs late impacts HRQOL. 4. To evaluate safety by AEs monitoring and relevant clinical laboratory parameters (hematology and chemistry.

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Part 1: 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 10 to 14 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).
2. Part 2: 1. Patient must be >CR and MRD negative measured by Euroflow NGF after 1.L therapy. The cutoff for inclusion into part 2 will be < 0.001% clonal plasma cells monitored in BM. Patients included directly into part 2 must have a MRD negative test which is less than one month old from time of testing after consolidation to screening for part 2. 2. Norway: Has received 1.L treatment in part 1 of the study or has received ASCT as part of 1.L treatment outside the REMNANT study. Countries outside Norway: Has received 1.L treatment including ASCT according to local guidelines. 3. ECOG performance status score 0, 1 or 2 4. Must have measurable disease at diagnosis

Exclusion criteria 2

1. Part 1: 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. An active malignancy with a lower life expectancy than myeloma 5. Female patient who has 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.
2. Part 2: 1. An 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. 3. Not refractory to daratumumab and/or carfilzomib

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: 1. The number of patients who achieve MRD negativity measured by Euroflow at 30-45 days after the 4th cycle of consolidation therapy has started.
2. Part 2: 1. PFS rate of Arm A (MRD guided) vs Arm B defined as the time from randomization to disease progression or death due to any cause following 2.L treatment. 2. OS rate of Arm A (MRD guided) vs Arm B defined as the time from randomization to death of any cause following 2.L treatment.

Secondary endpoints 2

1. Part 1: 1. The PFS rate of patients receiving 4 cycles of VRd as consolidation 2. The OS rate of patients receiving 4 cycles of VRd as consolidation 3. The number of AEs and relevant laboratory parameters monitored at every visit from entry into part 1 of the study until end of part 1 4. The proportion of patients who achieve PR or better following 4 cycles of VRd consolidation treatment
2. Part 2: 1.Time from randomization to start of 3.L therapy (TTNT) 2.The proportion of patients who achieve MRD negativity during 2.L treatment, monitored by MRD Euroflow at 6 and 18 months in arm A, and after achieving CR in arm B (first MRD testing after 6 months). 3.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. 4.The number of AEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Locations

2 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications