Clinical trial NCT06577025: 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
Official title: A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of Different Sequences of Ciltacabtagene Autoleucel (Cilta-cel), Talquetamab SC in Combination With Daratumumab SC (Tal-D) and Teclistamab SC in Combination With Daratumumab SC (Tec-D) Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) in Participants With Standard-risk Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of Response with Curative Potential
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS) Rate at 3-Year
timeFrame: At 3-year
measure: PFS Rate at 5-Year
timeFrame: At 5-year
Secondary outcomes:
measure: Overall response rate (ORR; Partial response [PR] or better)
timeFrame: Up to 5 years
measure: CR or Better Rate
timeFrame: Up to 5 years
measure: Very Good Partial Response (VGPR) or Better Rate
timeFrame: Up to 5 years
measure: Duration of Response (DOR)
timeFrame: Up to 5 years
measure: Time to First Response (TTR)
timeFrame: Up to 5 years
measure: Duration of CR or Better Response
timeFrame: Up to 5 years
measure: Time to First CR or Better Response
timeFrame: Up to 5 years
measure: PFS on next line therapy (PFS2)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: MRD-negative CR Rate
timeFrame: Up to 5 years
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity
timeFrame: Up to 5 years
measure: 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)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Salvador
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: