A Study of Ciltacabtagene Autoleucel and Talquetamab for the Treatment of Participants With High-Risk Multiple Myeloma
- Conditions
- Interventions
- Registration Number
- NCT06550895
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to define the safety of Ciltacabtagene Autoleucel (Cilta-cel) and Talquetamab in participants with high-risk multiple myeloma (MM).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Documented diagnosis of MM according to the IMWG diagnostic criteria and is defined as a measurable disease at screening
- Cohorts 1 and 3: Received at least 3 prior lines of antimyeloma therapy and have undergone greater than or equal to (>=) 1 complete cycle of the therapy. Cohort 2: Be newly diagnosed MM and considered ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT)
- Cohorts 1 and 3: Documented evidence of progression of disease (PD) or failure to achieve a response to the last line of therapy
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Participant of childbearing potential (POCBP) must have a negative pregnancy test using a highly sensitive β-human chorionic gonadotropin (hCG) serum pregnancy test at screening
- Cohorts 1 and 3: Prior treatment with chimeric antigen receptor T cell (CAR-T) therapy directed at any target or any prior B cell maturation antigen (BCMA)-directed therapy/prior G protein-coupled receptor family C Group 5 member D (GPRC5D)-directed therapy. Cohort 2: Received any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
- Cohorts 1 and 3: Received either of the following: An allogenic stem cell transplant within 6 months before apheresis/first dose of study drug and no immunosuppressive medications administered before the start of study treatment. And secondly, received an autologous stem cell transplant less than (<)12 weeks before apheresis/first dose of study treatment
- Cohort 2: Received a strong cytochrome P450 (CYP450) inducer within 5 half-lives prior to daratumumab, lenalidomide and dexamethasone (DRd) induction therapy
- Receive live, attenuated vaccine within 4 weeks of enrollment
- Toxicity from previous anticancer therapy not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy Cilta-cel Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 1: Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T)Therapy Cilta-cel Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered Cilta-cel followed by multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 1: Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T)Therapy Talquetamab Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered Cilta-cel followed by multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 3: Tal Bridging Therapy Pre-CAR-T Therapy + Cilta-cel Cilta-cel Participants with RRMM will receive multiple cycles of talquetamab bridging therapy followed by cilta-cel therapy and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy Daratumumab Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy Talquetamab Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy Lenalidomide Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy Dexamethasone Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. Cohort 3: Tal Bridging Therapy Pre-CAR-T Therapy + Cilta-cel Talquetamab Participants with RRMM will receive multiple cycles of talquetamab bridging therapy followed by cilta-cel therapy and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AE) by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Up to 3 years and 5 months An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non-investigational) product. It does not necessarily have a causal relationship with the investigational product. The severity of AEs has 5 grades based on NCI-CTCAE version 5.0 criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Lif...
- Secondary Outcome Measures
Name Time Method Overall Survival Up to 3 years and 5 months Overall Survival is measured from the date of the first study treatment to the date of the participant's death.
Percentage of Participants with Minimal Residual Disease (MRD) Negativity Up to 3 years and 5 months The percentage of participants who achieve MRD-negativity at a threshold of 10\^-5 at any timepoint after the date of the first study treatment and before disease progression or start of any subsequent antimyeloma therapy will be reported.
Percentage of Participants with Sustained MRD-Negativity Up to 3 years and 5 months The percentage of participants who sustained MRD-negative status, as determined by next generation sequencing (NGS) with sensitivity of 10\^-5, for at least 6 months without examination showing MRD-positive or PD in between will be reported.
Percentage of Participants With Overall Response (OR) Up to 3 years and 5 months The percentage of participants who have a partial response (PR) or better response according to the International Myeloma Working Group (IMWG) response criteria will be reported.
Percentage of Participants with Very Good Partial Response (VGPR) or Better Up to 3 years and 5 months The percentage of participants who achieve a VGPR or better response according to the IMWG response criteria will be reported.
Percentage of Participants with Complete Response (CR) or Stringent Complete Response (sCR) Up to 3 years and 5 months The percentage of participants with best overall response of CR or sCR will be reported according to IMWG criteria.
Duration of Response (DOR) Up to 3 years and 5 months DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD) (defined in the IMWG response criteria) or death due to any cause, whichever occur first.
Time to Response (TTR) Upto 3 years and 5 months TTR is defined as the time between date of the first study treatment and the first efficacy evaluation that the participant met all criteria for PR or better.
Progression Free Survival (PFS) Up to 3 years and 5 months PFS is defined as the time from the date of the first study treatment to the date of first documented disease progression (defined in the IMWG response criteria), or death due to any cause, whichever occurs first.
Trial Locations
- Locations (12)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Medical College Of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Austin Hospital
🇦🇺Heidelberg, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia