Minimal Residual Disease-based Strategy with T-Cell Redirector After Treatment with Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) in Newly Diagnosed Multiple Myeloma: A Phase 2 (IFM 2022-01).
- Conditions
- Multiple myelomaTherapeutic area: Not possible to specify
- Registration Number
- CTIS2023-508310-41-00
- Lead Sponsor
- Centre Hospitalier Universitaire De Nantes
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 103
Male or female patients must be at least 18 years of age at the time of consent younger than 66 years., A male patient must wear a condom (with spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a period of 6 months after the last dose of study treatments. If the male patient’s partner is a female of childbearing potential, she must also be practicing a highly effective method of contraception (see Appendix 1). NOTE: If the male patient is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception., Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care., Willing and able to adhere to the lifestyle restrictions specified in this protocol., Affiliation with French social security system or beneficiary from such system., A male patient must agree not to donate sperm for the purpose of reproduction during the study and for a period of 6 months after receiving the last dose of study. Male patients should consider preservation of sperm prior to study treatment as anti cancer treatments may impair fertility., Documented multiple myeloma satisfying the CRAB criteria and measurable disease as defined by: a.Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma AND any one or more of the following myeloma defining events: i.Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than ULN or >2.75 mmol/L (>11 mg/dL) ii.Renal insufficiency: creatinine clearance <40 mL/min (as calculated by the Cockcroft-Gault, see Appendix 6) or serum creatinine >177 µmol/L (>2 mg/dL) iii.Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL (Hemoglobin measurement performed as part of standard of care within 42 days before enrollment is acceptable for screening for CRAB criteria; but must be performed within 28 days before enrollment for other eligibility requirements) iv.Bone lesions: one or more osteolytic lesions on skeletal radiography, CT or PET-CT (PET-CT=18F-fluorodeoxyglucose positron emission tomography with computed tomography. If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement). v.Clonal bone marrow plasma cell percentage =60% (Clonality should be established by showing ?/?-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used). vi.Involved: uninvolved serum free light chain ratio =100 (These values are based on the serum Freelite assay [The Binding Site Group, Birmingham, UK]. The involved free light chain must be =100 mg/L.) vii.>1 focal lesion on MRI studies (Each focal lesion must be 5 mm or more in size.) b.Measurable disease at Screening as defined by any of the following: i.Serum M-protein level =0.5 g/dL; or ii.Urine M-protein level =200 mg/24 hours; or iii.Serum Ig FLC =10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. Source: Rajkum
Medical Conditions 1.Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI CTCAE Version 5.0., 10. Presence of the following cardiac conditions: a.New York Heart Association stage III or IV congestive heart failure (Appendix 10) b.Myocardial infarction or coronary artery bypass graft =6 months prior to enrollment c.History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d.Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities e.History of severe non-ischemic cardiomyopathy, 11.Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as: a.Acute diffuse infiltrative pulmonary disease a.Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy b.History of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing. c.Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status. d.Any other issue that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. e.History of noncompliance with recommended medical treatments, 12.Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug (daratumumab, bortezomib, lenalidomide, dexamethasone, teclistamab or talquetamab) or its excipients (refer to the appropriate IBs and SmPCs) or analogues and study–required co-medication., 13.Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs., Prior/Concomitant Therapy 14.Prior or current systemic therapy or SCT 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., 15.Received a strong CYP3A4 inducer within 5 half-lives prior to the first dose of study treatment (Flockhart 2016: http://medicine.iupui.edu/flockhart/)., 16.Plasmapheresis within 28 days prior to the first dose of study treatment., 17.Patient had major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the patient is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment. NOTE: Patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question whether a procedure is considered a major surgery, the investigator must consult with the appropriate Sponsor representative and resolve any issues before enrolling a patient in the study., 18.Taken any disallowed therapies as noted in Section 6.8, Concomitant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method