Phase 2 Study Applying MRD Techniques for Participants With Previously Untreated Multiple Myeloma Treated With D-VRd Prior To and After High-dose Therapy Followed by ASCT - TAURUS
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT06189833
- Lead Sponsor
- Stichting European Myeloma Network
- Brief Summary
This is a multicenter, single arm, open-label, Phase 2 study in mutiple myeloma with newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan. The study is evaluating a technique called Mass Spectrometry Minimal Residual Disease (MS-MRD) using blood samples and compares it with the minimal residual disease (MRD) technique using bone marrow samples.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 18 to 70 years of age, inclusive.
- Must have a new diagnosis of MM as per IMWG criteria.
- Measurable disease
- Newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
- Clinical laboratory values meeting the required criteria during screening and ≤3 days prior to receiving first study treatment dose.
- Adequate bone marrow function.
- Adequate liver function.
- Adequate renal function.
- A female of childbearing potential (FOCBP) must have two negative serum or urine pregnancy tests at screening including within 24 hours of the start of study treatment.
- Willing to practicing at least 1 highly effective method of contraception starting 4 weeks prior to start of study treatment, while receiving study treatment including during any dose interruptions, and for at least 3 months after the last dose of any component of the study treatment.
- Prior or current systemic therapy or ASCT for any plasma cell dyscrasia, with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
- History of allogenic stem cell transplantation or prior organ transplant requiring immunosuppressive therapy.
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.
- Myelodysplastic syndrome or any malignancy within 24 months of signing consent. The only exceptions are malignancies treated within the last 24 months that are considered completely cured.
- Plasmapheresis ≤28 days of approval.
- Radiation therapy for treatment of plasmacytoma ≤14 days of approval of enrollment.
- Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal.
- Concurrent medical or psychiatric condition or disease.
- Myocardial infarction ≤6 months of enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
- Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities.
- Allergy, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients of daratumumab, lenalidomide, bortezomib or dexamethasone.
- Pregnant or breast-feeding females
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description D-VRd + ASCT + DVRD Daratumumab Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation. Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6 D-VRd + ASCT + DVRD Bortezomib Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation. Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6 D-VRd + ASCT + DVRD Lenalidomide Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation. Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6 D-VRd + ASCT + DVRD Dexamethasone Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation. Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6
- Primary Outcome Measures
Name Time Method Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGS-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-consolidation. Up to 12 months The proportion (%) of agreement will be defined as the total number of concordant cases (i.e., MRD-positive by both techniques, MRD-negative by both techniques) versus the total number of cases with available results.
- Secondary Outcome Measures
Name Time Method Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGF-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-induction and post-consolidation. Up to 12 months The proportion (%) of agreement will be defined as the total number of concordant cases (i.e., MRD-positive by both techniques, MRD-negative by both techniques) versus the total number of cases with available results.
ORR, VGPR or better, CR or better, sCR at post-induction, post-transplant, post-consolidation and overall. Up to 12 months ORR will be defined as the percentage of participants achieving confirmed PR or better (i.e., PR+VGPR+CR+sCR). The number and percentage of participants achieving ORR, VGPR or better, CR or better and sCR will be presented, post-induction, post-consolidation, post-transplant and overall.
Proportion (%) of agreement and disagreement in the MRD measurements in BM by NGF-MRD and NGS-MRD at post-induction and post-consolidation. Up to 12 months The proportion (%) of agreement will be defined as the total number of concordant cases (i.e., MRD-positive by both techniques, MRD-negative by both techniques) versus the total number of cases with available results.
MRD negativity rate BM-MRD and PB-MRD Up to 12 months To evaluate the MRD negativity rate achieved at any time up to the end of consolidation with BM based MRD techniques and with the MS-MRD technique
Effect of cytogenetic abnormalities (presence or not), R-ISS (1, 2 or 3), CTCs (number of cells per ml) on likelihood to develop MRD-negative disease (with MS, NGS and NGF) and the agreement between the different techniques. Up to 12 months Binary logistic regression will be used to identify factors associated with post-induction and post-consolidation MRD status (negative or positive) (as defined with NGS-MRD; NGF-MRD; MS-MRD; the most conservative method), in the MRD-evaluable Analysis Set. Odds ratios and respective 95% CIs will be estimated from univariable and multivariable models.
Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGS-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-induction. Up to 4 months and 2 weeks The proportion (%) of agreement will be defined as the total number of concordant cases (i.e., MRD-positive by both techniques, MRD-negative by both techniques) versus the total number of cases with available results.
Trial Locations
- Locations (31)
St Savvas Cancer Hospital
🇬🇷Athens, Greece
Universitätsklinikum Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Innsbruck Medical University
🇦🇹Innsbruck, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
A.O.Spedali Civili di Brescia
🇮🇹Brescia, Italy
A.O. S. Santa Maria Hospital Institute of Oncohematology Terni
🇮🇹Terni, Italy
AOU Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Ospedale S. Maria della Misericordia di Udine
🇮🇹Udine, Italy
Amphia ziekenhuis
🇳🇱Breda, Netherlands
Ordensklinikum Linz
🇦🇹Linz, Austria
Klinikum rechts der Isar (MRI) der Technischen Universität München Department of Internal Medicine III (Hematology/Oncology) Munchen
🇩🇪München, Germany
A.O.U. di Bologna - Policlinico S. Orsola Malpighi
🇮🇹Bologna, Italy
A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U
🇮🇹Torino, Italy
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Maasstad Ziekenhuis
🇳🇱Rotterdam, Netherlands
Clinic Ottakring
🇦🇹Vienna, Austria
University Hospital of Alexandroupolis
🇬🇷Alexandroupolis, Greece
Theagenion Cancer Hospital
🇬🇷Thessaloníki, Greece
Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
🇬🇷Athens, Greece
A.O.U. Careggi - Firenze
🇮🇹Firenze, Italy
Policlinico S. Matteo Fondazione IRCCS - Pavia
🇮🇹Pavia, Italy
Novara Hospital
🇮🇹Novara, Italy
AUSL-IRCCS di Reggio Emilia Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
Ospedale "Infermi" di Rimini
🇮🇹Rimini, Italy
Ematologia IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo
🇮🇹San Giovanni Rotondo, Italy
Erasmus University Medical Center Rotterdam
🇳🇱Rotterdam, Netherlands
Dijklander ziekenhuis
🇳🇱Purmerend, Netherlands
ASST Papa Giovanni XXIII Hospital
🇮🇹Bergamo, Italy
A.O.U. Policlinico S. Martino - Ematologia
🇮🇹Genova, Italy
Amsterdam Medical Center
🇳🇱Amsterdam, Netherlands
Rijnstate
🇳🇱Arnhem, Netherlands