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)
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
N/A
Intervention / Treatment
Study Design
Treatment
N/A
Single Group Assignment
None (Open Label)
Arm Groups
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.
Eligibility 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.
- 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
Outcome Measures
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
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
Where is this study conducted?
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