This is Phase 2, open-label, multicentre, non-randomised study evaluating participants with newly diagnosed MM eligible for high-dose therapy. The goal of the study is to determine if consolidation with T-cell redirectors - Talquetamab and Teclistamab in sequence will improve the response depth: increase MRD negative CR rate.
A total of 50 transplant-eligible patients with newly diagnosed multiple myeloma in need of treatment will be enrolled. The study consists of three phases: Induction, Consolidation, and Follow-up. Induction will consist of Dara-VRd and consolidation Part I will include talquetamab and Part II will include teclistamab. Follow-up Phase After consolidation, treatment continues upon physician's choice: the options are ASCT with maintenance or only maintenance with lenalidomide. Efficacy will be evaluated by serum/urine electrophoresis monthly; by serum/urine immunofixation, bone marrow morphology and flow cytometry when CR/sCR is suspected; MRD will be evaluated by NGS ( at the level of 10-6) and FDG PET-CT ( by Deauville score) at various timepoints during induction, consolidation and follow-up. Participants quality of life, symptoms, functional and general well-being will be captured using 3 PRO measures ( PRO-CTCAE, EORTC QLQ-C30, FACT-Cog). The safety of study drugs will be assessed by physical examinations, vital signs, ECGs, clinical laboratory tests, neurologic examinations (including ICE scores), ECOG performance status, and AE monitoring according to NCI-CTCAE Version 5.0), grading of CRS and ICANS will be assessed based on ASTCT guidelines.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Daratumumab will be administered by SC injection
Bortezomib will be administered by SC injection
Lenalidomide will be administered by oral route
Copenhagen University Hospital (Rigshospitalet)
Copenhagen, Denmark
NOT_YET_RECRUITINGOdense University Hospital
Odense, Denmark
NOT_YET_RECRUITINGVejle hospital
Vejle, Denmark
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by next generation sequencing ( NGS) after completing consolidation with talquetamab and teclistamab.
MRD measured by NGS with a sensitivity level of 10-6.
Time frame: 18 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing consolidation with talquetamab and teclistamab.
MRD assessed by FDG PET-CT scan using Deauville score.
Time frame: 18 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by next generation sequencing ( NGS) after completing induction treatment with Daratumumab-VRd
MRD measured by NGS with a sensitivity level of 10-6.
Time frame: 6 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing induction treatment with Daratumumab-VRd.
MRD assessed by FDG PET-CT scan using Deauville score.
Time frame: 6 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by next generation sequencing ( NGS) after completing consolidation treatment with talquetamab.
MRD measured by NGS with a sensitivity level of 10-6.
Time frame: 12 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing consolidation treatment with talquetamab.
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Dexamethasone will be administered by oral route
Talquetamab will be administered by SC injection
Teclistamab will be administered by SC injection
North Estonia Medical Centre
Tallinn, Estonia
RECRUITINGOslo University Hospital, Oslo Myeloma Centre
Oslo, Norway
NOT_YET_RECRUITINGStavanger University Hospital
Stavanger, Norway
NOT_YET_RECRUITINGSt. Olavs Hospital
Trondheim, Norway
NOT_YET_RECRUITINGMRD assessed by FDG PET-CT scan using Deauville score.
Time frame: 12 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by next generation sequencing ( NGS) after completing consolidation treatment with teclistamab.
MRD measured by NGS with a sensitivity level of 10-6.
Time frame: 18 months approximately
Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing consolidation treatment with teclistamab.
MRD assessed by FDG PET-CT scan using Deauville score.
Time frame: 18 months approximately
Evaluate efficacy in terms of Sustained Minimal Residual Disease (MRD) negative Complete Remission rate by next generation sequencing ( NGS).
MRD measured by NGS with a sensitivity level of 10-6.
Time frame: 42 months approximately
Evaluate efficacy in terms of Sustained Minimal Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan.
MRD assessed by FDG PET-CT scan using Deauville score.
Time frame: 42 months approximately
To assess Overall Response Rate (ORR)
ORR is defined as proportion of patients achieveing documentation of a response (Partial Response or better) from the first dose of study drug on treatment. Response to treatment is defined according to the International Myeloma Working Group (IMWG) criteria.
Time frame: 42 months approximately
To assess Overall Survival (OS).
OS is defined as the time from the date of first dose of study drug to the date of the subject's death. If the subject is alive or the vital status is unknown, then the subject's data will be censored at the date the subject was last known to be alive. OS is measured in months.
Time frame: 42 months approximately
To assess Progression free Survival (PFS).
PFS is defined as the time from the date of first dose of study drug to the date of first documented disease progression, as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. PFS is measured in months.
Time frame: 42 months approximately
To assess Duration of Response ( DoR).
DoR is the date of initial documentation of a response (Partial Response or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. Relapse from complete response is not considered as disease progression. For subjects who have not progressed, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. DoR is measured in months.
Time frame: 42 months approximately
To assess Time to Next anti-myeloma Treatment (TNT).
TNT is defined as the time between date of first dose of study drug and the first dose of the next treatment received. TNT is measured in months.
Time frame: 42 months approximately
To assess the safety and tolerability of the treatment described in the protocol.
Incidence of treatment-emergent adverse events. AE monitoring according to NCI-CTCAE Version 5.0), grading of CRS and ICANS will be assessed based on ASTCT guidelines.
Time frame: 42 months approximately
To assess quality of life on the treatment described in the protocol.
Quality of life in general is assessed using PRO questionnaire, such as EORTC QLQ-C30.
Time frame: 42 months approximately
To assess incidence of participant -recorded side effects on the treatment described in the protocol.
Participant - recorded side effects are assessed using PRO questionnaire, such as PRO-CTCAE.
Time frame: 42 months approximately