LCAR-M61S and LCAR-M61D in Treatment of Relapsed/Refractory Multiple Myeloma
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Biological: LCAR-M61S cells preparationBiological: LCAR-M61D cells preparation
- Registration Number
- NCT06472479
- Brief Summary
A prospective, two-cohort, open-label dose-exploration and expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61S and LCAR-M61D in patients with relapsed/refractory multiple myeloma.
- Detailed Description
This study was a prospective, two-cohort, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61S and LCAR-M61D in patients with relapsed/refractory multiple myeloma. All subjects who meet the eligibility criteria will receive intravenous injection of LCAR-M61S or LCAR-M61D cell injection. The study will include the following sequential phases: screening, apheresis, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 66
- Subjects voluntarily participate in clinical research;
- Age ≥18 years old;
- Eastern Cooperative Oncology Group (ECOG) score 0-2;
- Examination evidence of initial diagnosis of MM according to IMWG diagnostic criteria;
- Measurable lesions were present;
- Subjects have received at least three previous lines of multiple myeloma therapy, each with at least one complete therapy cycle, unless the best response to the therapeutic regimen was documented as disease progression (PD confirmed according to IMWG criteria);
- Expected survival ≥3 months;
- Clinical laboratory values in the screening period meet criteria;
- Received previous therapy targeting GPRC5D and/or CD19 targets;
- Prior antineoplastic therapy and meet exclusion criteria (before apheresis);
- Subjects had Waldenstrom macroglobulinemia, POEMS syndrome, or primary AL amyloidosis at the time of screening.
- Subjects who were positive for any of HBsAg, HBV DNA, HCV-Ab, HCV RNA, and HIV-Ab;
- Life-threatening allergic reactions, hypersensitivity reactions, or intolerance to CAR-T cell formulations or their excipients, including DMSO, are known.
- Serious underlying diseases were present;
- Female subjects who were pregnant, breastfeeding, or planning to become pregnant while participating in this study or within 1 year of receiving study treatment.
- Also enrolled in other clinical studies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LCAR-M61S and LCAR-M61D LCAR-M61S cells preparation Each subject will be given a single-dose LCAR-M61S or LCAR-M61D cells infusion at each dose level. LCAR-M61S and LCAR-M61D LCAR-M61D cells preparation Each subject will be given a single-dose LCAR-M61S or LCAR-M61D cells infusion at each dose level.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity (DLT) rate From LCAR-M61S and LCAR-M61D cell preparations infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days DLT was classified according to the NCI-CTCAE V5.0 toxicity evaluation criteria and ASTCT consensus classification within 30 days after dose infusion (D1-D30), which was considered by the investigator or collaborator to be reasonably related to LCAR-M61S or LCAR-M61D cell therapy.
Time to Cmax (Tmax) From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years The time it takes to reach the maximum concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time to the last observed concentration (Tlast) From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years The time it takes to reach the last observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Incidence, severity, and type of treatment-emergent adverse events (TEAEs) From the date of signing ICF to the date (2 years after LCAR-M61S and LCAR-M61D cell preparation infusion (Day 1) An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
To determine the recommended dose for phase II clinical trials (RP2D) Through the last subject of DLT exploration completion, about 2 years RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design
Maximum concentration (Cmax) From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years The maximum observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Area Under the Curve (AUC) of the concentration From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years The exposure of CAR positive T cells or transgene CAR copy number in peripheral blood experienced by the subject in a certain time interval.
- Secondary Outcome Measures
Name Time Method Progression-free survival（PFS） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years According to International Myeloma Working Group (IMWG) efficacy criteria.PFS was defined as the interval from the date of the first infusion of the LCAR-M61S or LCAR-M61D cells preparation to the first documentation of disease progression (according to IMWG criteria) or death from any cause, whichever occurred first.
Objective Response Rate (ORR) From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years According to International Myeloma Working Group (IMWG) efficacy criteria.ORR was defined as the proportion of patients with PR or better response after infusion of LCAR-M61S or LCAR-M61D cells.
Stringent complete response（sCR） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years Proportion of subjects achieving sCR according to IMWG criteria.
Minimal residual disease (MRD) negative rate From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years Proportion of subjects achieving minimal residual disease (MRD) negative rate according to IMWG criteria.
Overall survival（OS） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years According to International Myeloma Working Group (IMWG) efficacy criteria.Overall survival (OS) was defined as the interval from the date of the first infusion of LCAR-M61S or LCAR-M61D cells preparation to death.
Occurrence rate of antidrug antibody From LCAR-M61S or LCAR-M61D cells preparation infusion until the date of first documented progression or study completion，assessed about 2 years Occurrence rate of LCAR-M61S or LCAR-M61D cells preparation ADA
Very Good Partial Response Rate（VGPR） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years Proportion of subjects achieving VGPR according to IMWG criteria.
Complete response（CR） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years Proportion of subjects achieving CR according to IMWG criteria.
Time-to-response（TTR） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years According to International Myeloma Working Group (IMWG) efficacy criteria.TTR was defined as the interval from the date of the first infusion of the LCAR-M61S or LCAR-M61D cells preparation to the date of the first efficacy assessment for which the subject met all criteria for PR or better. Analyses were performed only in responders.
Duration of response（DOR） From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years According to International Myeloma Working Group (IMWG) efficacy criteria. DOR was defined as the time from the first documented response (PR or better response) to the first documented evidence of disease progression (as defined according to IMWG criteria) or death from any cause .
Trial Locations
- Locations (4)
Beijing Gobroad Hospital
🇨🇳Beijing, China
Anhui Cancer Hospital
🇨🇳Hefei, Anhui, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China