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

NCT ID: NCT06577025

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-20

Study Completion Date

2030-09-02

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

Cilta-cel

Intervention Type DRUG

Cilta-cel infusion will be administered intravenously.

Talquetamab

Intervention Type DRUG

Talquetamab will be administered subcutaneously.

Daratumumab

Intervention Type DRUG

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

Bortezomib

Intervention Type DRUG

Bortezomib will be administered subcutaneously as a part of induction.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered orally as a part of induction.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally as a part of induction.

Cyclophosphamide

Intervention Type DRUG

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

Fludarabine

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

Cilta-cel

Intervention Type DRUG

Cilta-cel infusion will be administered intravenously.

Talquetamab

Intervention Type DRUG

Talquetamab will be administered subcutaneously.

Daratumumab

Intervention Type DRUG

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

Teclistamab

Intervention Type DRUG

Teclistamab will be administered subcutaneously.

Bortezomib

Intervention Type DRUG

Bortezomib will be administered subcutaneously as a part of induction.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered orally as a part of induction.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally as a part of induction.

Cyclophosphamide

Intervention Type DRUG

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

Fludarabine

Intervention Type DRUG

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

Interventions

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Cilta-cel

Cilta-cel infusion will be administered intravenously.

Intervention Type DRUG

Talquetamab

Talquetamab will be administered subcutaneously.

Intervention Type DRUG

Daratumumab

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

Intervention Type DRUG

Teclistamab

Teclistamab will be administered subcutaneously.

Intervention Type DRUG

Bortezomib

Bortezomib will be administered subcutaneously as a part of induction.

Intervention Type DRUG

Lenalidomide

Lenalidomide will be administered orally as a part of induction.

Intervention Type DRUG

Dexamethasone

Dexamethasone will be administered orally as a part of induction.

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Fludarabine

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

Intervention Type DRUG

Other Intervention Names

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JNJ-68284528, Ciltacabtagene autoleucel JNJ-64407564 JNJ-54767414 JNJ-64007957

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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City of Hope

Duarte, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

The Alfred Hospital

Melbourne, , Australia

Site Status

Instituto D Or de Pesquisa e Ensino

Salvador, , Brazil

Site Status

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, , Brazil

Site Status

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, , Brazil

Site Status

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Site Status

Universitatsklinikum Wurzburg

Würzburg, , Germany

Site Status

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Site Status

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Site Status

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Site Status

Countries

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United States Australia Brazil Germany Spain

Other Identifiers

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54767414MMY2093

Identifier Type: OTHER

Identifier Source: secondary_id

2023-505792-71-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

54767414MMY2093

Identifier Type: -

Identifier Source: org_study_id