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Trial Title: GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5

NCT ID: NCT05695508

Condition: Multiple Myeloma

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Lenalidomide
Bortezomib
Daratumumab

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: Induction Treatment of Arms A, A1, B, D, E, E1, F, F1 contain 6 cycles of Tec-DRd [Arm A, A1, D] , Tec-DVRd [Arm B], Tal-DRd [Arm E, E1] or Tal-DVRd [Arm F, F1]. Enrollment will be staggered with Arm A opening first. Induction therapy (except Arm D) is followed by HDT and a single ASCT according to local SoC. After ASCT, participants will receive maintenance treatment with Tec-D [Arm A, A1, B, E. F] or Tal-D [E1, F1] Arm C and C1 participants will enter the study at Maintenance Treatment with Tec-D or Tal-DR after induction, HDT, and ASCT according to local SoC (outside of the study). All Arms will receive maintenance treatment for a max. of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. An optional end of treatment is possible for those patients who have sustained MRD negativity of 12 months. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Teclistamab (Tec)
Description: Subcutaneous administration of Teclistamab
Arm group label: Arm A Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm A1 Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm group label: Arm C Tec-D Maintenance
Arm group label: Arm D Tec-DRd Induction and Tec-Tal following induction
Arm group label: Arm E Tal-DRd Induction and Tec-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance

Other name: JNJ-64007957

Intervention type: Drug
Intervention name: Daratumumab
Description: Subcutaneous administration of Daratumumab
Arm group label: Arm A Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm A1 Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm group label: Arm C Tec-D Maintenance
Arm group label: Arm C2 Tal-DR Maintenance
Arm group label: Arm D Tec-DRd Induction and Tec-Tal following induction
Arm group label: Arm E Tal-DRd Induction and Tec-D Maintenance
Arm group label: Arm E1 Tal-DRd Induction and Tal-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Intervention type: Drug
Intervention name: Dexamethasone
Description: administered i.v. or orally
Arm group label: Arm A Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm A1 Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm group label: Arm D Tec-DRd Induction and Tec-Tal following induction
Arm group label: Arm E Tal-DRd Induction and Tec-D Maintenance
Arm group label: Arm E1 Tal-DRd Induction and Tal-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Intervention type: Drug
Intervention name: Lenalidomide
Description: Administration oral
Arm group label: Arm A Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm A1 Tec-DRd Induction and Tec-D Maintenance
Arm group label: Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm group label: Arm C2 Tal-DR Maintenance
Arm group label: Arm D Tec-DRd Induction and Tec-Tal following induction
Arm group label: Arm E Tal-DRd Induction and Tec-D Maintenance
Arm group label: Arm E1 Tal-DRd Induction and Tal-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Intervention type: Drug
Intervention name: Bortezomib
Description: Subcutaneous administration
Arm group label: Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Intervention type: Drug
Intervention name: Talquetamab
Description: Subcutaneous administration of Daratumumab
Arm group label: Arm C2 Tal-DR Maintenance
Arm group label: Arm D Tec-DRd Induction and Tec-Tal following induction
Arm group label: Arm E Tal-DRd Induction and Tec-D Maintenance
Arm group label: Arm E1 Tal-DRd Induction and Tal-D Maintenance
Arm group label: Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm group label: Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Summary: Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab- and Talquetamab-based Combination Regimens in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma OBJECTIVES: The primary objective is 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 The key secondary objective is 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

Detailed description: OVERALL DESIGN: 130 participants will be enrolled with 10 participants in Arm A, 20 participants in Arm A1, 20 participants in Arm B, 10 participants in Arms C and 10 in C2, 20 participants in Arm D, 10 participants in each Arm E, E1 and optionally F and F1. Cohorts may be further expanded. Arms A, A1, B, D, E, E1, F, F1 will receive Induction Therapy of 6 cycles (28-days each): Treatment: Tec-DRd (Arm A, A1), Tec-DVRd (Arm B), Tal-DRd (Arms E, E1), Tal-DVRd (Arms F, F1) followed by HDT and a single ASCT according to local SoC treatment. Thereafter a Maintenance Therapy of maximum 18 cycles with either Tec-D (Arms A, A1, B, E, F) or Tal-D (E1, F1) is performed. Arm D will receive Tec-DVRd induction followed by 18 cycles Tec-Tal. No HDT ASCT will be performed in Arm D. In Arm C and C2 participants will enter the study for maintenance treatment of 18 cycles with Tec-D (Arm C) or Tal-DR (Arm C2) , after induction, HDT and ASCT according to local SoC (outside of the study). Participants will receive maintenance treatment or following induction treatment (Arm D) for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. An optional end of treatment is possible for patients who have 12 months sustained MRD negativity. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable. Upon treatment discontinuation, an EOT Visit will be conducted. Thereafter, the participant will continue in the Follow-up Phase until death, withdrawal of consent, loss to follow-up, or end of the study, whichever occurs first.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 18 years of age to 70 years of age, inclusive - Have an ECOG performance status score of 0 to 2 at screening - Have clinical laboratory values meeting prespecified criteria during the Screening Phase. Participants in Arms A, A1, B, D, E, E1, F and F1 must also satisfy all of the following criteria to be enrolled in the study: 1. Documented multiple myeloma requiring treatment as defined by the criteria below: 1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria 2. 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 free light chain ratio 2. Newly diagnosed participants for whom HDT and ASCT is part of the intended treatment plan (except Arm D participants). Participants Arm C and C2 must also satisfy all of the following criteria: 1. Newly diagnosed multiple myeloma according to IMWG criteria. 2. Must have received 4 to 6 cycles of 3 or 4 drug-induction therapy that includes a proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody and a single or tandem ASCT. Post-ASCT consolidation is permitted for up to 2 cycles as long as the total number of induction plus consolidation cycles does not exceed 6. 3 Must have received only one line of therapy and achieved at least a PR as per IMWG 2016 without evidence of progression at the time of enrollment. 4. Must have received HDT and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT (7 months for participants who received consolidation) at the time of enrollment. Exclusion Criteria: - CNS involvement or clinical signs of meningeal involvement of multiple myeloma. - Stroke or seizure within 6 months prior study start Cycle1 Day1. - History of transplantations requiring immunosuppressive therapy. - Seropositive for HIV, HEP B, Active Hep C infection (details see protocol). - COPD with a FEV1 <50% of predicted normal. - Moderate /severe persistent asthma within the past 2 years or any uncontrolled asthma. Exclude if FEV1 <50% of predicted normal. - Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures, or that in the investigators opinion would constitute a hazard for participants. - Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug/excipients. - Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of any study treatment regimen. - Plans to father a child while enrolled in this study or within 100 days after the last dose of any component of the study treatment regimen. Arm A, A1, B, D, E, E1, F, F1 - Prior or current systemic therapy or stem cell transplant 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. - Arm B only: Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by the NCI-CTCAE Version 5. Due to a potential interaction with bortezomib, received a strong CYP3A4 inducer within 5 half-lives prior to enrollment Arm C and C2 - Discontinued treatment due to any AE related to lenalidomide as determined by the investigator. - Progressed on multiple myeloma therapy at any time prior to screening. - Received a cumulative dose of corticosteroids equivalent to ≥40 mg of dexamethasone within the 14 day period before the start of study treatment administration. - Intolerant to the starting dose of lenalidomide (10 mg). For further details on inclusion/exclusion criteria please refer to the study protocol.

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: Charité University Medicin Berlin

Address:
City: Berlin
Zip: 12203
Country: Germany

Status: Recruiting

Facility:
Name: Clinic Chemnitz gGmbH

Address:
City: Chemnitz
Zip: 09113
Country: Germany

Status: Recruiting

Facility:
Name: University Clinic Technical University Dresden

Address:
City: Dresden
Zip: 01307
Country: Germany

Status: Recruiting

Facility:
Name: University Clinic Düsseldorf

Address:
City: Düsseldorf
Zip: 40225
Country: Germany

Status: Recruiting

Facility:
Name: University Clinic Freiburg

Address:
City: Freiburg
Zip: 79106
Country: Germany

Status: Recruiting

Facility:
Name: Hamburg University Clinic Eppendorf

Address:
City: Hamburg
Zip: 20246
Country: Germany

Status: Recruiting

Facility:
Name: Asklepios Clinic Hamburg Altona

Address:
City: Hamburg
Zip: 22763
Country: Germany

Status: Recruiting

Facility:
Name: University Hospital Heidelberg

Address:
City: Heidelberg
Zip: 69120
Country: Germany

Status: Recruiting

Contact:
Last name: Marc S Raab

Facility:
Name: University Clinic Schleswig-Holstein Campus Kiel

Address:
City: Kiel
Zip: 24105
Country: Germany

Status: Recruiting

Facility:
Name: Technical University Munich

Address:
City: Munich
Zip: 81675
Country: Germany

Status: Recruiting

Facility:
Name: University Würzburg

Address:
City: Würzburg
Country: Germany

Status: Recruiting

Start date: December 1, 2022

Completion date: August 15, 2028

Lead sponsor:
Agency: University of Heidelberg Medical Center
Agency class: Other

Collaborator:
Agency: Janssen Research & Development, LLC
Agency class: Industry

Collaborator:
Agency: Deutsche Studiengruppe Multiples Myelom (DSMM)
Agency class: Other

Source: University of Heidelberg Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05695508

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