Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Multiple myeloma, Relapsed/Refractory multiple myeloma
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.
Interventions
BIOLOGICALLCAR-M61S cells preparation
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.
BIOLOGICALLCAR-M61D cells preparation
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.
Sponsors
Nanjing Legend Biotech Co.
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group Assignment & Two-cohort; LCAR-M61S and LCAR-M61D cells preparation intravenous infusion; Pretreatment of cyclophosphamide and fludarabine.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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;
Exclusion criteria
* Received previous therapy targeting GPRC5D and/or CD19 targets; * Prior antineoplastic therapy and meet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 . |
Countries
China
Contacts
Primary ContactLijuan Chen
Backup ContactXuxing Shen
Outcome results
None listed