A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma

NCT06577025 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 54767414MMY20932023-505792-71-00
• Study Type: interventional
• Target: 43
• Locations: 5 countries
• Sites: 16

Brief Summary

The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Rate of Response with Curative Potential

  Rate of Response with curative potential is defined as the percentage of participants with a composite of durable (at least 2 years) minimal residual disease (MRD) (10\^-5) negativity with complete response/stringent complete response (CR/sCR) by serology and negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years after start of induction therapy. This includes: negative imaging at 5-year landmark time; MRD-negative status (at 10\^-5) in 2 bone marrow examinations that are a minimum of 2 years apart; response of CR or better per the International Myeloma Working Group (IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between assessments.

  Up to 5 years

• Progression Free Survival (PFS) Rate at 3-Year

  PFS is defined as the time from the date of randomization to either progressive disease (PD), according to the IMWG response criteria, or death, whichever occurs first.

  At 3-year

• PFS Rate at 5-Year

  PFS is defined as the time from the date of randomization to either PD, according to the IMWG response criteria, or death, whichever occurs first.

  At 5-year

Secondary Outcomes (12)

• Overall response rate (ORR; Partial response [PR] or better)

  Up to 5 years

• CR or Better Rate

  Up to 5 years

• Very Good Partial Response (VGPR) or Better Rate

  Up to 5 years

• Duration of Response (DOR)

  Up to 5 years

• Time to First Response (TTR)

  Up to 5 years

Study Arms (2)

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel

EXPERIMENTAL

Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is of 28 days) and cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release, and completion of induction, participants will begin consolidation with 4 cycles of Tal-D (each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen.

Drug: Cilta-cel; Drug: Talquetamab; Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine

Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

EXPERIMENTAL

Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release and completion of induction, participants will begin consolidation with a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D (Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D or Tec-D is 84 days which includes an extended treatment-free interval.

Drug: Cilta-cel; Drug: Talquetamab; Drug: Daratumumab; Drug: Teclistamab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Cilta-cel DRUG

Cilta-cel infusion will be administered intravenously.

Also known as: JNJ-68284528, Ciltacabtagene autoleucel

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Talquetamab DRUG

Talquetamab will be administered subcutaneously.

Also known as: JNJ-64407564

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Fludarabine DRUG

Fludarabine will be administered intravenously as a part of conditioning regimen.

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Daratumumab DRUG

Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D or Tec-D consolidation.

Also known as: JNJ-54767414

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Teclistamab DRUG

Teclistamab will be administered subcutaneously.

Also known as: JNJ-64007957

Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Bortezomib DRUG

Bortezomib will be administered subcutaneously as a part of induction.

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Lenalidomide DRUG

Lenalidomide will be administered orally as a part of induction.

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Dexamethasone DRUG

Dexamethasone will be administered orally as a part of induction.

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Cyclophosphamide DRUG

Cyclophosphamide will be administered intravenously as a part of conditioning regimen.

Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation

Eligibility Criteria

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

You may qualify if:

• Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria and with no prior myeloma-directed therapy
• Participants must have standard-risk MM (stage I and II) based on revised International Staging System (R-ISS)
• Participants must be considered fit (score equals to \[=\] 0) or intermediate-fit (score=1) according to IMWG Frailty Index assessment (based on the Charlson Comorbidity Index, the Katz Activity of Daily Living and the Lawson Instrumental Activities of Daily Living)
• Measurable disease defined as: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) (\>=10 gram per liter \[g/L\] for institutions using alternative units) or urine M-protein level \>= 200 milligrams per 24 hours (mg/24 hours); Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain \>=10 milligrams per deciliter (mg/dL) (\>=100 mg/L for institutions using alternative units) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 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
• Peripheral neuropathy or neuropathic pain of Grade \>= 2, as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Known active or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM
• Stroke or seizure within 6 months of signing the informed consent form (ICF)
• Plasma cell leukemia at the time of diagnosis or any time thereafter through apheresis (\>= 5 percent \[%\] circulating plasma cells in peripheral blood smears), Waldenstrom macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes(POEMS) syndrome, or primary amyloid light chain amyloidosis with associated organ dysfunction
• Presence of high-risk disease features: (a) Cytogenetic high risk lesions by MM fluorescence in situ hybridization (FISH) including deletion 17p (del\[17p\])/, t(4;14), t(14;16), amplification 1q (amp\[1q21\]) (\>= 4 copies); (b) Presence of 1 or more extramedullary plasmacytomas
• Seropositive for human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (16)

City of Hope

Duarte, California, 91010, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Instituto D Or de Pesquisa e Ensino

Salvador, 41253 190, Brazil

Location

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

Location

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, 05652 900, Brazil

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

talquetamab; daratumumab; Bortezomib; Lenalidomide; Dexamethasone; Cyclophosphamide; fludarabine

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2024
• First Posted: August 29, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): September 2, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); ES (3); AU (2); US (5); BR (3)