Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma
NCT Number: NCT06574126
Acronym: CAR-HiRiSMM
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: High Risk Smoldering Multiple Myeloma
Interventions: DRUG: Group 1: Dara-VRD followed by apheresis and cilta-cel infusion|DRUG: Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion
Sponsor: PETHEMA Foundation
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 20
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-30
Completion Date: 2032-09-30

Summary:
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients.

The primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population; ii) to annotate frequency and severity of adverse events (AE) and serious adverse events (SAE), as well as data from laboratory tests aslo related with safety such as Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia adn T-cell populations. Secondary objectives are related with response to therapy and will measure different categories of response and survival.

Primary Outcome Measures: Proportion of patients with undetectable minimal residual disease (MRD), To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5. Undetectable MRD is defined as \<0,001% of bone marrow MM plasma cells/bone marrow normal plasma cells., 5 Years|Adverse events, To annotate the nature, frequency, severity, and timing of adverse events (AEs) and serious adverse events (SAEs), and discontinuations due to AEs or SAEs., 5 Years|Safety laboratory tests Immunoglobulin, To measure the Immunoglobulin (Ig) G levels. The units of measure for the immunoglobulin levels determinations will be g/L., 5 years|Safety laboratory tests CBC, To measure the complete blood count (CBC) cytopenia. The units of measure for the CBC determinations will be cells\*109/L., 5 years|Safety laboratory tests T-cells, To measure the cluster of differentiation 4 (CD4+) T lymphocytes (T-cells). The units of measure for the immunoglobulin levels determinations of will be cells\*109/L., 5 years
Secondary Outcome Measures: Response rate, To evaluate the overall response rate (ORR) as well as different response categories partial response (PR), very good partial response (VGPR), complete response (CR), and stringent CR (sCR), and duration of response (DOR), according to clinical judgement guided by the International Myeloma Working Group (IMWG) consensus recommendations for multiple myeloma treatment response criteria.

ORR is defined as the proportion of subjects who achieve a partial response (PR) or better according to the IMWG criteria after infusion of cilta-cel., 5 Years|Overall Survival, To assess the survival (OS) of patients with high-risk SMM. OS is defined as the time from the date of the initial infusion of cilta-cel to the date of the subject's death. If the subject is alive or the vital status is unknown, then the subject's data will be censored at the date the subject was last known to be alive., 5 Years|Progression-Free Survival, To assess progression free survival (PFS) of patients with high-risk SMM. PFS is defined as the time from the date of the first administration of study treatment to the date of first documented disease progression to myeloma defining events, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy., 5 Years