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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05695508

Studienbeginn:
Dezember 2022

Letztes Update:
28.11.2023

Wirkstoff:
Teclistamab (Tec), Daratumumab, Dexamethasone, Lenalidomide, Bortezomib

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
University of Heidelberg Medical Center

Collaborator:
Janssen Research & Development, LLC, Deutsche Studiengruppe Multiples Myelom (DSMM),

Kontakt

Marc S Raab, Prof. Dr. med
Kontakt:
Phone: +49 6221 56
Phone (ext.): 8198
E-Mail: s.gmmg@med.uni-heidelberg.de» Kontaktdaten anzeigen

Studienlocations
(3 von 11)

Charité University Medicin Berlin
12203 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps

Clinic Chemnitz gGmbH
09113 Chemnitz
(Sachsen)
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University Clinic Technical University Dresden
01307 Dresden
(Sachsen)
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University Clinic Düsseldorf
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

University Clinic Freiburg
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Hamburg University Clinic Eppendorf
20246 Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps

Asklepios Clinic Hamburg Altona
22763 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps

University Hospital Heidelberg
69120 Heidelberg
(Baden-Württemberg)
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University Clinic Schleswig-Holstein Campus Kiel
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps

Technical University Munich
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps

University Würzburg
Würzburg
(Bayern)
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Alle anzeigen

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. number of incidence and severity of adverse events [safety and tolerability] (Time Frame - through study completion, up to 28 months)

Secondary outcome:

1. MRD negativity rate (Time Frame - 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)):
MRD negativity rate measured by Flow Cytometry

2. Response on therapy [efficacy] (Time Frame - 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)):
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)

3. Progression Free Survival [efficacy] (Time Frame - From randomization to the date of disease progression to death (app. up to 3-4 years))

4. Serum concentration of teclistamab and daratumumab [pharmacokinetics] (Time Frame - through study completion, up to 28 months)

5. Presence of ADAs to teclistamab and daratumumab [immunogenicity] (Time Frame - through study completion, up to 28 months)

6. Stem cell yield (Time Frame - after High Dose Therapy (after app. 10 months)):
feasibility of successful transplantation

7. days to engraftment (Time Frame - after High Dose Therapy (after app. 10 months)):
feasibility of successful transplantation

Studien-Arme

Experimental: Arm A Tec-DRd Induction and Tec-DR Maintenance
Arm A participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC and lenalidomide in maximum 18 cycles of maintenance therapy.
Experimental: Arm B Tec-DVRd Induction and Tec-DR Maintenance
Arm B participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide, dexamethasone and bortezomib in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC and lenalidomide in maximum 18 cycles of maintenance therapy.
Experimental: Arm C Tec-DR Maintenance
Arm C participants will receive maximum 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.
Experimental: Arm A1 Tec-DRd Induction and Tec-DR Maintenance
Arm A participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC and lenalidomide in maximum 18 cycles of maintenance therapy.
Experimental: Arm C1 Tec-DR Maintenance
Arm C participants will receive maximum 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.

Geprüfte Regime

Teclistamab (Tec) (JNJ-64007957):
Subcutaneous administration of Teclistamab
Daratumumab:
Subcutaneous administration of Daratumumab
Dexamethasone:
administered i.v. or orally
Lenalidomide:
Administration oral
Bortezomib:
Subcutaneous administration

Quelle: ClinicalTrials.gov

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