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

Multiple Myeloma Clinical Trial

— TAURUS  

Official title:

Phase 2 Study Applying Innovative Minimal Residual Disease (MRD) Techniques for Participants With Previously Untreated Multiple Myeloma Treated With D-VRd Prior To and After High-dose Therapy Followed by Autologous Stem Cell Transplantation (ASCT) - TAURUS

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06189833
• Other study ID #: EMN33/54767414MMY2089
• Status: Recruiting
• Phase: Phase 2
• Start date: November 23, 2023
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Stichting European Myeloma Network
• Contact: Rosita Ghiraw-Visser
• Phone: +31 10 703 31 23
• Email: rosita.ghiraw[@]emn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab
Daratumumab will be administered via a subcutaneous injection (SC)
• Bortezomib
Bortezomib will be administered via a subcutaneous injection (SC)
• Lenalidomide
Lenalidomide will be administered orally
• Dexamethasone
Dexamethasone will be administered orally

Locations

Country	Name	City	State
Austria	Innsbruck Medical University	Innsbruck
Austria	Ordensklinikum Linz	Linz
Austria	Clinic Ottakring	Vienna
Austria	Medical University of Vienna	Vienna
Germany	Universitätsklinikum Hamburg - Eppendorf	Hamburg
Germany	Klinikum rechts der Isar (MRI) der Technischen Universität München Department of Internal Medicine III (Hematology/Oncology) Munchen	München
Greece	University Hospital of Alexandroupolis	Alexandroupolis
Greece	Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens	Athens
Greece	St Savvas Cancer Hospital	Athens
Greece	Theagenion Cancer Hospital	Thessaloníki
Italy	AOU Ospedali Riuniti di Ancona	Ancona
Italy	ASST Papa Giovanni XXIII Hospital	Bergamo
Italy	A.O.U. di Bologna - Policlinico S. Orsola Malpighi	Bologna
Italy	A.O.Spedali Civili di Brescia	Brescia
Italy	A.O.U. Careggi - Firenze	Firenze
Italy	A.O.U. Policlinico S. Martino - Ematologia	Genova
Italy	Novara Hospital	Novara
Italy	Policlinico S. Matteo Fondazione IRCCS - Pavia	Pavia
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	A.O. S. Santa Maria Hospital Institute of Oncohematology Terni	Terni
Italy	A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U	Torino
Italy	Ospedale S. Maria della Misericordia di Udine	Udine
Netherlands	Amsterdam Medical Center	Amsterdam
Netherlands	Rijnstate	Arnhem
Netherlands	Amphia ziekenhuis	Breda
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Dijklander ziekenhuis	Purmerend
Netherlands	Erasmus University Medical Center Rotterdam	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Stichting European Myeloma Network	Janssen Pharmaceutica

Countries where clinical trial is conducted

Austria,  Germany,  Greece,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	Up to 12 months
Secondary	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.	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.	Up to 4 months and 2 weeks
Secondary	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.	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.	Up to 12 months
Secondary	Proportion (%) of agreement and disagreement in the MRD measurements in BM by NGF-MRD and NGS-MRD at post-induction and post-consolidation.	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.	Up to 12 months
Secondary	MRD negativity rate BM-MRD and PB-MRD	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	Up to 12 months
Secondary	ORR, VGPR or better, CR or better, sCR at post-induction, post-transplant, post-consolidation and overall.	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.	Up to 12 months
Secondary	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.	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.	Up to 12 months