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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Biological: LCAR-M61S or LCAR-M61D cells intravenous infusion; Prior to infusion of the LCAR-M61S and LCAR-M61D cell preparation, Subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.
Biological: LCAR-M61S or LCAR-M61D cells intravenous infusion; Prior to infusion of the LCAR-M61S and LCAR-M61D cell preparation, Subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.
Anhui Cancer Hospital
Hefei, Anhui, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Jiangsu Province Hospital
Nanjing, Jiangsu, China
Beijing Gobroad Hospital
Beijing, China
Dose-limiting toxicity (DLT) rate
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 frame: From LCAR-M61S and LCAR-M61D cell preparations infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
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.
Time frame: From the date of signing ICF to the date (2 years after LCAR-M61S and LCAR-M61D cell preparation infusion (Day 1)
To determine the recommended dose for phase II clinical trials (RP2D)
RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design
Time frame: Through the last subject of DLT exploration completion, about 2 years
Maximum concentration (Cmax)
The maximum observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time frame: 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
Time to Cmax (Tmax)
The time it takes to reach the maximum concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time frame: 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time to the last observed concentration (Tlast)
The time it takes to reach the last observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time frame: 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
Area Under the Curve (AUC) of the concentration
The exposure of CAR positive T cells or transgene CAR copy number in peripheral blood experienced by the subject in a certain time interval.
Time frame: 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
Objective Response Rate (ORR)
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.
Time frame: 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
Very Good Partial Response Rate（VGPR）
Proportion of subjects achieving VGPR according to IMWG criteria.
Time frame: 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
Complete response（CR）
Proportion of subjects achieving CR according to IMWG criteria.
Time frame: 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
Stringent complete response（sCR）
Proportion of subjects achieving sCR according to IMWG criteria.
Time frame: 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
Minimal residual disease (MRD) negative rate
Proportion of subjects achieving minimal residual disease (MRD) negative rate according to IMWG criteria.
Time frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years
Time-to-response（TTR）
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.
Time frame: 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
Duration of response（DOR）
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 .
Time frame: 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
Progression-free survival（PFS）
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.
Time frame: 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
Overall survival（OS）
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.
Time frame: 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
Occurrence rate of antidrug antibody
Occurrence rate of LCAR-M61S or LCAR-M61D cells preparation ADA
Time frame: From LCAR-M61S or LCAR-M61D cells preparation infusion until the date of first documented progression or study completion，assessed about 2 years