Multiple Myeloma
Conditions
Keywords
MS-MRD
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.
Interventions
DRUGDaratumumab
Daratumumab will be administered via a subcutaneous injection (SC)
DRUGBortezomib
Bortezomib will be administered via a subcutaneous injection (SC)
DRUGLenalidomide
Lenalidomide will be administered orally
DRUGDexamethasone
Dexamethasone will be administered orally
Sponsors
Janssen Pharmaceutica
Stichting European Myeloma Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Austria, Germany, Greece, Italy, Netherlands
Contacts
Primary ContactRosita Ghiraw-Visser
Outcome results
None listed