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
