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 (TAURUS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone; Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rosita Ghiraw-Visser; Phone Number: +31 10 703 31 23; Email: rosita.ghiraw@emn.org

Study Locations

• Austria
  • Innsbruck, Austria
    • Not yet recruiting
    • Innsbruck Medical University
    • Contact: Willenbacher
  • Linz, Austria
    • Recruiting
    • Ordensklinikum Linz
    • Contact: Strassl
  • Vienna, Austria
    • Not yet recruiting
    • Clinic Ottakring
    • Contact: Schreder
  • Vienna, Austria
    • Not yet recruiting
    • Medical University of Vienna
    • Contact: Krauth
• Germany
  • Hamburg, Germany
    • Recruiting
    • Universitätsklinikum Hamburg - Eppendorf
    • Contact: Weisel
  • München, Germany
    • Not yet recruiting
    • Klinikum rechts der Isar (MRI) der Technischen Universität München Department of Internal Medicine III (Hematology/Oncology) Munchen
    • Contact: Basserman
• Greece
  • Alexandroupolis, Greece
    • Recruiting
    • University Hospital of Alexandroupolis
    • Contact: Spanoudakis
  • Athens, Greece
    • Recruiting
    • St Savvas Cancer Hospital
    • Contact: Pouli
  • Athens, Greece
    • Recruiting
    • Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
    • Contact: Evangelos Terpos
  • Thessaloníki, Greece
    • Recruiting
    • Theagenion Cancer Hospital
    • Contact: Katodritou
• Italy
  • Ancona, Italy
    • Recruiting
    • AOU Ospedali Riuniti di Ancona
    • Contact: Offidani
  • Bergamo, Italy
    • Recruiting
    • ASST Papa Giovanni XXIII Hospital
    • Contact: Rambaldi
  • Bologna, Italy
    • Not yet recruiting
    • A.O.U. di Bologna - Policlinico S. Orsola Malpighi
    • Contact: Zamagni
  • Brescia, Italy
    • Recruiting
    • A.O.Spedali Civili di Brescia
    • Contact: Belotti
  • Firenze, Italy
    • Recruiting
    • A.O.U. Careggi - Firenze
    • Contact: Antonioli
  • Genova, Italy
    • Not yet recruiting
    • A.O.U. Policlinico S. Martino - Ematologia
    • Contact: Aquino
    • Principal Investigator: Aquino
  • Novara, Italy
    • Recruiting
    • Novara Hospital
    • Contact: Margiotta Casaluci
  • Pavia, Italy
    • Recruiting
    • Policlinico S. Matteo Fondazione IRCCS - Pavia
    • Contact: Mangiacavalli
  • Reggio Emilia, Italy
    • Recruiting
    • AUSL-IRCCS di Reggio Emilia Arcispedale S. Maria Nuova
    • Contact: Gamberi
  • Rimini, Italy
    • Recruiting
    • Ospedale "Infermi" di Rimini
    • Contact: Tosi
  • San Giovanni Rotondo, Italy
    • Recruiting
    • Ematologia IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo
    • Contact: Falcone
  • Terni, Italy
    • Not yet recruiting
    • A.O. S. Santa Maria Hospital Institute of Oncohematology Terni
    • Contact: Liberati
  • Torino, Italy, 10126
    • Recruiting
    • A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U
    • Contact: Mina
  • Udine, Italy
    • Not yet recruiting
    • Ospedale S. Maria della Misericordia di Udine
    • Contact: Patriarca
• Netherlands
  • Amsterdam, Netherlands
    • Not yet recruiting
    • Amsterdam Medical Center
    • Contact: Van der Donk
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate
    • Contact: Van der Spek
  • Breda, Netherlands
    • Not yet recruiting
    • Amphia Ziekenhuis
    • Contact: van der Klift
    • Principal Investigator: van der Klift
  • Groningen, Netherlands
    • Not yet recruiting
    • University Medical Center Groningen
    • Contact: Roeloffzen
  • Purmerend, Netherlands
    • Recruiting
    • Dijklander Ziekenhuis
    • Contact: Klerk
  • Rotterdam, Netherlands
    • Recruiting
    • Maasstad Ziekenhuis
    • Contact: Sprenger
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Erasmus University Medical Center Rotterdam
    • Contact: Wester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: D-VRd + ASCT + DVRD; 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

Drug: Lenalidomide; Lenalidomide will be administered orally; Drug: Daratumumab; Daratumumab will be administered via a subcutaneous injection (SC); Other Names: JNJ-54767414; Drug: Dexamethasone; Dexamethasone will be administered orally; Drug: Bortezomib; Bortezomib will be administered via a subcutaneous injection (SC); Other Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Stichting European Myeloma Network
• Collaborators: Janssen Pharmaceutica

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 20, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MS-MRD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Daratumumab; Bortezomib
• Other Study ID Numbers: EMN33/54767414MMY2089

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes