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

Phase 2

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Cilta-cel; Drug: Talquetamab; Drug: Daratumumab; Drug: Bortezomib; Drug: Teclistamab; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT06577025
• Lead Sponsor: Janssen Research & Development, LLC

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...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2024-08-20
• Study First Submitted: 2024-08-27
• Study First Submitted QC: 2024-08-27
• Study First Posted: 2024-08-29
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Primary Completion: 2030-07-31
• Study Completion: 2030-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria
• 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) 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) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

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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 screening (>= 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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Bortezomib	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Talquetamab	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Lenalidomide	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Dexamethasone	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.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Cilta-cel	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Daratumumab	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Fludarabine	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.
Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel	Cyclophosphamide	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.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Talquetamab	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Daratumumab	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Teclistamab	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Bortezomib	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Dexamethasone	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Cyclophosphamide	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Lenalidomide	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 and Tec-D is 84 days which includes an extended treatment-free interval.
Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation	Fludarabine	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 and Tec-D is 84 days which includes an extended treatment-free interval.

Primary Outcome Measures

Name	Time	Method
Rate of Response with Curative Potential	Up to 5 years	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...
Progression Free Survival (PFS) Rate at 3-Year	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.
PFS Rate at 5-Year	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.

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR; Partial response [PR] or better)	Up to 5 years	ORR (PR or better) is defined as the percentage of participants with best overall response of PR or better according to IMWG response criteria.
CR or Better Rate	Up to 5 years	Rate of CR or better is defined as the percentage of participants with best overall response of CR or better according to IMWG response criteria.
Very Good Partial Response (VGPR) or Better Rate	Up to 5 years	Rate of VGPR or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria.
Duration of Response (DOR)	Up to 5 years	DOR is calculated among responders (with a PR or better response) from the date of initial documented response (PR or better) to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first.
Time to First Response (TTR)	Up to 5 years	Time to response (that is, time to first response) is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better based on the computerized algorithm per IMWG criteria for those who had PR or better as their best response.
Duration of CR or Better Response	Up to 5 years	Duration of CR or better response is calculated among responders (with a CR or better response) from the date of initial documented response CR or better to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first.
Time to First CR or Better Response	Up to 5 years	Time to first CR or better response is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for CR or better based on the computerized algorithm per IMWG criteria.
PFS on next line therapy (PFS2)	Up to 5 years	PFS2 is defined as time from randomization to progression on the next line of therapy or death, whichever comes first.
Overall Survival (OS)	Up to 5 years	OS is measured from the date of randomization to the date of death due to any cause.
MRD-negative CR Rate	Up to 5 years	MRD-negative CR is defined as the percentage of participants who achieved both CR or better and MRD negativity at a threshold of 10\^-5 and 10\^-6. MRD-negative CR rate will be evaluated at the first occurrence from induction treatment initiation for participants per IMWG criteria.
Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity	Up to 5 years	An Adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity of TEAEs will be graded according t...
Change from baseline in Health-related quality of life (HRQoL) (symptoms and functioning) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 item instrument (EORTC-QLQ-C30)	Up to 5 years	Change from baseline in participants' HRQoL (symptoms and functioning) as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetit...

Trial Locations

Locations (8)

Hosp Clinico Univ de Salamanca; 🇪🇸 Salamanca, Spain

Hosp. Univ. Marques de Valdecilla; 🇪🇸 Santander, Spain

City of Hope; 🇺🇸 Duarte, California, United States

University of Iowa Hospital and Clinics; 🇺🇸 Iowa City, Iowa, United States

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Australia

Fundacao Antonio Prudente A C Camargo Cancer Center; 🇧🇷 Sao Paulo, Brazil

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein; 🇧🇷 Sao Paulo, Brazil