GMMG-HD11/DSMM XXI/64007957MMY3010

NCT07671287 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: GMMG-HD11/DSMM-XXI2025-523990-40-00
• Study Type: interventional
• Target: 399
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, randomized interventional multicenter Phase 3 clinical trial to investigate the efficacy and safety of Tec-DRd induction therapy and fixed-duration Tec-D maintenance post ASCT in adult participants with TE NDMM, compared with the SoC PERSEUS regimen. A total of 399 participants with TE NDMM aged ≥18 and ≤70 years and an Eastern CooperativeOncology Group (ECOG) status 0-2 will be included. The primary objective of the clinical trial: To determine the efficacy of Tec-DRd compared to DVRd after 6 cycles of induction/consolidation therapy and HD melphalan and ASCT, before start of maintenance therapy in participants with TE NDMM. Endpoint: Cumulative MRD negativity by NGS at a sensitivity level of 10-6 before start of maintenance therapy.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy (MRD negativity at a level of 10-6) of Tec-DRd compared to DVRd after induction/consolidation therapy and HD melphalan and ASCT, before start of maintenance therapy in participants with TE NDMM

  Cumulative MRD negativity by NGS at a sensitivity level of 10-6 before start of maintenance therapy.

  after 6 cycles (each cycle is 28 days) of induction/consolidation therapy and HD melphalan and ASCT (which occurs appr. 1 year after start of treatment), before start of maintenance therapy.

Secondary Outcomes (2)

• Sustained MRDnegative CR rate composite endpoint of events (death, progression, discontinuation of all treatments, Grade 3 or Grade 4 infections, and pause of more than 62 days of all study treatments).

  1) up to 24 months of maintenance therapy. 2) within 24 months of maintenance therapy

• To determine response rates, MRD at a level of 10-5, best overall response and DOR, PFS, OS, stem cell harvest.

  up to 24 months of maintenance

Study Arms (3)

Arm A DVRd induction (+ HDT ASCT), DVRd consolidation therapy followed by DR maintenance

ACTIVE COMPARATOR

SoC treatment based on the PERSEUS regimen - control): DVRd induction therapy, HD melphalan + ASCT, DVRd consolidation therapy, followed by DR maintenance therapy. After the maintenance therapy, the participant will be treated according to SoC.

Drug: Daratumumab; Drug: Lenalidomide; Drug: Bortezomib (B); Drug: dexamethsone

Arm B - Tec-DRd induction ( incl. HDT ASCT) followed by DR maintenance therapy.

EXPERIMENTAL

Tec-DRd induction therapy, HD melphalan + ASCT, followed by DR maintenance therapy. Treatment stopped thereafter.

Drug: Teclistamab; Drug: Daratumumab; Drug: Lenalidomide; Drug: dexamethsone

Arm C - Tec-DRd induction (incl. HDT ASCT), followed by Tec-D then DR maintenance therapy

EXPERIMENTAL

Tec-DRd induction therapy, HD melphalan + ASCT, followed by Tec-D then DR maintenance therapy. Treatment stopped thereafter.

Drug: Teclistamab; Drug: Daratumumab; Drug: Lenalidomide; Drug: dexamethsone

Interventions

Teclistamab DRUG

TEC SC

Arm B - Tec-DRd induction ( incl. HDT ASCT) followed by DR maintenance therapy.; Arm C - Tec-DRd induction (incl. HDT ASCT), followed by Tec-D then DR maintenance therapy

Daratumumab DRUG

subcutaneous

Arm A DVRd induction (+ HDT ASCT), DVRd consolidation therapy followed by DR maintenance; Arm B - Tec-DRd induction ( incl. HDT ASCT) followed by DR maintenance therapy.; Arm C - Tec-DRd induction (incl. HDT ASCT), followed by Tec-D then DR maintenance therapy

Lenalidomide DRUG

oral administration

Arm A DVRd induction (+ HDT ASCT), DVRd consolidation therapy followed by DR maintenance; Arm B - Tec-DRd induction ( incl. HDT ASCT) followed by DR maintenance therapy.; Arm C - Tec-DRd induction (incl. HDT ASCT), followed by Tec-D then DR maintenance therapy

Bortezomib (B) DRUG

subcutaneous

Arm A DVRd induction (+ HDT ASCT), DVRd consolidation therapy followed by DR maintenance

dexamethsone DRUG

iv; po

Arm A DVRd induction (+ HDT ASCT), DVRd consolidation therapy followed by DR maintenance; Arm B - Tec-DRd induction ( incl. HDT ASCT) followed by DR maintenance therapy.; Arm C - Tec-DRd induction (incl. HDT ASCT), followed by Tec-D then DR maintenance therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 70 years of age, inclusive.
• Documented MM as defined by the criteria below:
• MM diagnosis according to IMWG diagnostic criteria (Appendix 3),
• Untreated MM requiring systemic therapy,
• Measurable disease at screening, as defined by any of the following:
• i. Serum M-protein level ≥1.0 g/dL (central laboratory); or ii. Urine M-protein level ≥200 mg/24 hours (central laboratory); or iii. Serum immunoglobulin free light chain ≥10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Have an ECOG performance status 0-2 (Appendix 5) at screening and immediately prior to the start of administration of study treatment.
• Have clinical laboratory values meeting the following criteria during the screening period. Refer to Section 5.4.3 for criteria prior to first dose.
• Hemoglobin ≥7.5 g/dL (≥4.65 mmol/L; without prior RBC transfusion ≤7 days before the screening laboratory test; recombinant human erythropoietin use is permitted). Platelets ≥75×109/L in participants in whom \<50% of bone marrow nucleated cells are plasma cells and ≥50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells. 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 ≥14 days for pegylated-G-CSF) before the screening laboratory test.
• Chemistry:
• AST and ALT ≤3×ULN. Total bilirubin Total bilirubin ≤2.0×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case if total bilirubin is \>2.0×ULN, then direct bilirubin ≤1.5×ULN is required).
• eGFR ≥30 mL/min based on Cockcroft-Gault formula or creatine clearance measured by a 24-h urine collection. Serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L; see Appendix 10).
• Eligible for HD melphalan and ASCT (in the opinion of the investigator).
• A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
• A female participant must be (as defined in Appendix 1):

You may not qualify if:

• Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM).
• Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy.
• Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than MM. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured:
• Nonmuscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, \<3 cm, no carcinoma in situ).
• Nonmelanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone.
• Noninvasive cervical cancer.
• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (antihormonal therapy is permitted).
• Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (radical prostatectomy/radiation therapy/focal treatment).
• Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor's medical monitor.
• Plasma cell leukemia (presence of ≥5% circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic MM; Fernández de Larrea 2021), smoldering MM, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), primary light chain amyloidosis.
• CNS involvement or clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain MRI and lumbar cytology are required to exclude CNS involvement.
• Prior BCMA-directed therapy.
• Prior T-cell redirection therapy.
• History of allogeneic or autologous stem cell transplant or prior organ transplant.
• Prior or concurrent exposure to any of the following within the specified timeframe prior to randomization:

Sponsors & Collaborators

• University of Heidelberg Medical Center: lead

Related Publications (1)

• Avet-Loiseau H, Davies FE, Samur MK, Corre J, D'Agostino M, Kaiser MF, Raab MS, Weinhold N, Gutierrez NC, Paiva B, Neri P, Weisel K, Maura F, Walker BA, Bustoros M, Stewart AK, Usmani SZ, Hillengass J, Chng WJ, Keats JJ, Martinez-Lopez J, Sperling AS, Touzeau C, Zhan F, Raje NS, Cavo M, Bolli N, Ghobrial IM, Dhodapkar MV, Jagannath S, Spencer A, Parekh S, Bahlis NJ, Lonial S, Sonneveld P, Bergsagel L, Orlowski RZ, Morgan G, Mateos MV, Rajkumar SV, San Miguel JF, Anderson KC, Moreau P, Kumar S, Prosper F, Munshi NC. International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma. J Clin Oncol. 2025 Aug 20;43(24):2739-2751. doi: 10.1200/JCO-24-01893. Epub 2025 Jun 9.

  PMID: 40489728 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Study Officials

• Marc S Raab, Prof. Dr. med

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc S Raab, Prof. Dr. med

CONTACT

+49 6221-56819; marc.raab@med.uni-.heidelberg.de

Lilli Podola, Dr.

CONTACT

+49 6221 567222; lilli.podola@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 26, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): February 14, 2031
• Study Completion (Estimated): January 30, 2033
• Last Updated: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share