Clinical trial NCT06472479: LCAR-M61S and LCAR-M61D in Treatment of Relapsed/Refractory Multiple Myeloma
Official title: A Clinical Study to Evaluate the Safety, Tolerance and Efficacy of LCAR-M61S and LCAR-M61D Cell Preparations in Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: Multiple myeloma
Relapsed/Refractory multiple myeloma
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2024-06-25
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment \& Two-cohort; LCAR-M61S and LCAR-M61D cells preparation intravenous infusion; Pretreatment of cyclophosphamide and fludarabine.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT) rate
timeFrame: From LCAR-M61S and LCAR-M61D cell preparations infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: From the date of signing ICF to the date (2 years after LCAR-M61S and LCAR-M61D cell preparation infusion (Day 1)
measure: To determine the recommended dose for phase II clinical trials (RP2D)
timeFrame: Through the last subject of DLT exploration completion, about 2 years
measure: Maximum concentration (Cmax)
timeFrame: 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
measure: Time to Cmax (Tmax)
timeFrame: 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
measure: Time to the last observed concentration (Tlast)
timeFrame: 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
measure: Area Under the Curve (AUC) of the concentration
timeFrame: 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
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Very Good Partial Response Rate（VGPR）
timeFrame: 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
measure: Complete response（CR）
timeFrame: 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
measure: Stringent complete response（sCR）
timeFrame: 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
measure: Minimal residual disease (MRD) negative rate
timeFrame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years
measure: Time-to-response（TTR）
timeFrame: 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
measure: Duration of response（DOR）
timeFrame: 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
measure: Progression-free survival（PFS）
timeFrame: 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
measure: Overall survival（OS）
timeFrame: 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
measure: Occurrence rate of antidrug antibody
timeFrame: From LCAR-M61S or LCAR-M61D cells preparation infusion until the date of first documented progression or study completion，assessed about 2 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Beijing
country: China
facility: Beijing Gobroad Hospital
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Lijuan Chen
role: PRINCIPAL_INVESTIGATOR
References: