GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5

Multiple Myeloma Clinical Trial

— HD10/DSMMXX  

Official title:

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination With Daratumumab, Lenalidomide, and Dexamethasone With or Without Bortezomib as Induction Therapy and Teclistamab in Combination With Daratumumab and Lenalidomide as Maintenance Therapy in Participants With Newly Diagnosed Transplant Eligible Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05695508
• Other study ID #: GMMG-HD10/DSMM-XX
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2022
• Est. completion date: October 15, 2027

Study information

• Verified date: November 2023
• Source: University of Heidelberg Medical Center
• Contact: Marc S Raab, Prof. Dr. med
• Phone: +49 6221 56
• Email: s.gmmg[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination with Daratumumab, Lenalidomide, and Dexamethasone with or without Bortezomib as Induction Therapy and Teclistamab in Combination with Daratumumab and Lenalidomide as Maintenance Therapy in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma. OBJECTIVES: The primary objective is to evaluate the safety and tolerability of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy in participants with ND-TEMM. The key secondary objective is to evaluate the efficacy of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy.

Description:

OVERALL DESIGN: 70 participants will be enrolled with approximately 10 participants in Arm A, 10 participants in Arm C, 40 participants in Arm A1 and Arm B (20 each Arm), and optionally 10 further participants in Arm C1 Arms A, A1 and B will receive Induction Therapy of 6 cycles (28-days each): Treatment: Tec-DRd (Arm A, A1) or Tec-DVRd (Arm B) followed by HDT and a single ASCT according to local SoC treatment. Thereafter a Maintenance Therapy of maximum 18 cycles with Tec-DR is performed. In Arm C and C1 participants will enter the study for maintenance treatment of 18 cycles with Tec-DR, after induction, HDT and ASCT according to local SoC (outside of the study). Participants will receive maintenance treatment with Tec-DR 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: October 15, 2027
• Est. primary completion date: October 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 Arm A, A1 and Arm B 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.

Participants Arm C and C1 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 3 months after the last dose of any component of the study treatment regimen. Arm A, A1 and B
• 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 C1
• 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Teclistamab (Tec)
Subcutaneous administration of Teclistamab
• Daratumumab
Subcutaneous administration of Daratumumab
• Dexamethasone
administered i.v. or orally
• Lenalidomide
Administration oral
• Bortezomib
Subcutaneous administration

Locations

Country	Name	City	State
Germany	Charité University Medicin Berlin	Berlin
Germany	Clinic Chemnitz gGmbH	Chemnitz
Germany	University Clinic Technical University Dresden	Dresden
Germany	University Clinic Düsseldorf	Düsseldorf
Germany	University Clinic Freiburg	Freiburg
Germany	Asklepios Clinic Hamburg Altona	Hamburg
Germany	Hamburg University Clinic Eppendorf	Hamburg
Germany	University Hospital Heidelberg	Heidelberg
Germany	University Clinic Schleswig-Holstein Campus Kiel	Kiel
Germany	Technical University Munich	Munich
Germany	University Würzburg	Würzburg

Sponsors (3)

Lead Sponsor	Collaborator
University of Heidelberg Medical Center	Deutsche Studiengruppe Multiples Myelom (DSMM), Janssen Research & Development, LLC

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of incidence and severity of adverse events [safety and tolerability]		through study completion, up to 28 months
Secondary	MRD negativity rate	MRD negativity rate measured by Flow Cytometry	after 6 cycles (each cycle is 28 days) induction therapy (app.month 6), after High Dose Therapy (app. month 10), after 18 cycles (each cycle is 28 days) of maintenance therapy (app. month 28)
Secondary	Response on therapy [efficacy]	Response on therapy according to IMWG: Overall Response Rate (ORR) (at least a PR or better); Complete Response (CR) or better; Very Good Partial Response (VGPR) or better; Duration of Response (DoR)	after each cycle (each cycle is 28 days) induction ( app. at month 1,2,...,6), after High Dose therapy (app. month 10), after each cycle (each cycle is 28 days) of maintenance (app. at month 11,12, ...28), during FU every 3 months (app. up to 3-4 years)
Secondary	Progression Free Survival [efficacy]		From randomization to the date of disease progression to death (app. up to 3-4 years)
Secondary	Serum concentration of teclistamab and daratumumab [pharmacokinetics]		through study completion, up to 28 months
Secondary	Presence of ADAs to teclistamab and daratumumab [immunogenicity]		through study completion, up to 28 months
Secondary	Stem cell yield	feasibility of successful transplantation	after High Dose Therapy (after app. 10 months)
Secondary	days to engraftment	feasibility of successful transplantation	after High Dose Therapy (after app. 10 months)