Newly Diagnosed Multiple Myeloma in patients eligible for stem cell transplantation MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Ruprecht-Karls-University Heidelberg, Medical Faculity, represented by University Hospital Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 to 70 years of age, inclusive 2. Have an ECOG performance status score of 0 to 2 at screening 3. Have clinical laboratory values meeting the following criteria during the Screening Phase. Hematology: Hemoglobin>=7.5 g/dL (>=4.65 mmol/L; without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted) Platelets: >=75×10E9/L in participants in whom =50×10E9/L in participants in whom =50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) Absolute neutrophil count: >=1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated-G-CSF) Chemistry AST, ALT: =2.5×ULN eGFR: =30 mL/min based on Cockcroft-Gault formula or a 24-hour urine collection Total bilirubin: =2.0×ULN; (isolated total bilirubin = 1.5 x ULN with conjugated [direct] bilirubin <1.5xULN is allowed for those participants with known congenital nonhemolytic hyperbilirubinemia such as Gilbert’s syndrome). Serum calcium corrected for albumin: =14 mg/dL (=3.5 mmol/L) or free ionized calcium =6.5 mg/dL (=1.6 mmol/L) 4. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening, and within 24 hours before start of study treatment, and must agree to further pregnancy tests during the study. 5. A participant must be either a. Not of childbearing potential, or b. Of childbearing potential and practicing 2 effective methods of contraception from the time of signing ICF until 6 months after the last dose of study treatment. Contraception must begin 4 weeks prior to dosing of lenalidomide. 6. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. 7. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 100 days after receiving the last dose of study treatment. 8. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 100 days after receiving the last dose of study treatment. 9. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol, including adherence to the global PPP or local PPP program for lenalidomide. 10. Must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. Participants in Arms A, A1, B, D, E, E1, F, F1 must also satisfy all of the following criteria to be enrolled in the study: 1A. Documented multiple myeloma as defined by the criteria below: a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria b. Measurable disease at screening as defined by any of the following: 1. Serum M-protein level =1.0 g/dL or 2. Urine M-protein level =200 mg/24 hours or 3. Serum immunoglobulin free light chain level =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio 2A. Newly diagnosed participants for whom HDT and ASCT is part of the intended treatment plan. Participants Arms C, C1; C2 must also sati
Exclusion criteria
Exclusion criteria: 1.a. Ongoing myelodysplastic syndrome or B-cell malignancy (other than MM) b. History of malignancy (other than MM), considered high risk of recurrence requiring systemic therapy. c. Active malignancy other than MM. Exceptions (details see protocol): - Non-muscle invasive bladder cancer - Non- melanoma skin cancer after curative therapy or localized melanoma after curative surgical resection alone - Non-invasive cervical cancer - Breast cancer: adequately treated lobular carcinoma in situ, or history of localized breast cancer - Localized prostate cancer, treated locally only 2. CNS involvement or clinical signs of meningeal involvement of MM. 3. Stroke, transient ischemic attack or seizure within 6 months prior C1D1. 4. History of allogeneic stem cell transplant or organ transplantations requiring immunosuppressive therapy. 5. Any of the following - Positive HIV, Hep B, active Hep C (details see protocol) - COPD with a FEV1 <50% of predicted normal. - Moderate/severe persistent asthma within the past 2 years or uncontrolled asthma. 6 Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures, or that in the investigator’s opinion would constitute a hazard for participants, such as: a. Acute diffuse infiltrative pulmonary disease b. Evidence of active systemic viral, fungal or bacterial infection, requiring systemic antimicrobial therapy c. History of autoimmune disease, exc. vitiligo, type I diabetes, prior autoimmune thyroid disease currently euthyroid d. Disabling psychiatric conditions, severe dementia, or altered mental status e. History of noncompliance 7. Following cardiac conditions: a. New York Heart Association stage III or IV congestive heart failure b. Myocardial infarction, unstable angina, or coronary artery bypass graft =6 months prior enrollment c. History of clinically significant ventricular arrhythmia or unexplained syncope d. Uncontrolled cardiac arrhythmia or clinically significant abnormal ECG. 8. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug/excipients. 9. Pregnant, breastfeeding, or planning pregnancy while enrolled in this study or within 6 months after the last dose of any study treatment. 10. Plans to father a child while enrolled in this study or within 100 days after the last dose of any study treatment. 11. significant traumatic injury or major surgery within 2 weeks prior to the start of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the study or within 2 weeks after the last dose of study treatment. 12. Received an investigational drug, used an invasive investigational medical device within 4 weeks or 5 half-lives of the respective drug/IMP before enrollment or is enrolled in an interventional study. 13. Have gastrointestinal disease that may significantly alter the absorption of oral drugs 14. Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment. 15. Be unable or unwilling to undergo antithrombotic prophylactic treatment. Arms A, A1, B. D, E, E1, F and F1 1. Prior or current systemic therapy or stem cell transplant for plasma cell dyscrasia, with the exc. of emergency use of a short course (equiv. of dexamethasone 40 mg/day for a max. 4 days) of corticosteroids before treatment. 2. Radiotherapy within 14 days or focal radiation within 7 days of enrollment. Radiotherapy on measurable soft-tissue plasmacy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of teclistamab- and talquetamab-based combination regimens over the entire treatment phase for each arm, in participants with ND-TEMM.;Secondary Objective: -To evaluate MRD negativity rates, conversion, and sustainability -To evaluate the efficacy of teclistamab- and talquetamab-based combination regimens as induction and post-transplant maintenance treatments, and teclistamab in combination with talquetamab as replacement for HDT+ASCT following induction: Post-induction, post-ASCT (Arms A, A1, B, E, E1 and, if applicable, F and F1), postmaintenance (Arms A, A1, B, E, E1 and, if applicable, F and F1), post-Tec-Tal (Arm D), and best overall: ORR (at least PR or better) CR or better VGPR or better - DOR - PFS -To assess feasibility of successful transplantation (all arms except Arm D) (Stem cell yield and days to engraftment) -To characterize the PK of teclistamab and talquetamab in participants with multiple myeloma before and after ASCT or during Tec-Tal treatment, and to characterize the PK of daratumumab after ASCT (population PK approach) -To assess the immunogenicity of teclistamab, talquetamab and daratumumab (ADA) ;Primary end point(s): Incidence and severity of AEs and SAEs;Timepoint(s) of evaluation of this end point: any time during the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate MRD negativity rates, conversion, and sustainability: Post-induction, post-ASCT, post-maintenance, and best overall - MRD negative CR Sustained MRD negative CR (duration =12 months) after 18 cycles of maintenance treatment MRD negative CR conversion and deepening during maintenance To evaluate the efficacy of Teclistamab and Talquetamab based combination regimes as induction and posttransplant maintenance treatments, and teclistamab in combination with talquetamab as replacement for ASCT following induction. Post-induction, post-ASCT (Arms A, A1, B, E, E1 and, if applicable, F and F1), postmaintenance (Arms A, A1, B, E, E1 and, ifapplicable, F and F1), post-Tec-Tal (Arm D), and best overall: - ORR (at least a PR or better) - CR or better - VGPR or better DOR PFS To assess feasibility of successful transplantation (all arms except ArmD): Stem cell yield and days to engraftment (all arms except Arm D) To characterize the PK of teclistamab and talquetamab in participants with multiple myeloma before and after an ASCT or during Tec-Tal treatment, and to characterize the PK of daratumumab after an ASCT: PK parameters using population PK approach To assess the immunogenicity of teclistamab, talquetamab and daratumumab: Measure presence of ADAs ;Timepoint(s) of evaluation of this end point: MRD negativity rates, conversion, and sustainability: Post-induction, post-ASCT, post-maintenance, and best overall Sustained MRD negative CR: =12 months and after 18 cycles of maintenance treatment. Sustained MRD negative CR - ORR (at least a PR or better) - CR or better - VGPR or better Post-induction, post-ASCT, post-maintenance (assessments 3-monthly), and best overall: DOR: 3-monthly response assessment PFS: 3-monthly response assessment PK analysis: over the course of the study | — |
Countries
Germany
Contacts
Public ContactGMMG Studiensekretariat
GMMG Study Office
Outcome results
None listed