An Exploratory Clinical Study on the Safety and Efficacy of YTS104 Cell Injection in the Treatment of Relapsed or Refractory Multiple Myeloma

Institute of Hematology & Blood Diseases Hospital, China1 site in 1 country12 target enrollmentJune 28, 2023

ConditionsRelapsed or Refractory Multiple Myeloma

InterventionsYTS104 Cells injection

DrugsYTS104 Cells injection

Overview

Phase: Phase 1
Intervention: YTS104 Cells injection
Conditions: Relapsed or Refractory Multiple Myeloma
Sponsor: Institute of Hematology & Blood Diseases Hospital, China
Enrollment: 12
Locations: 1
Primary Endpoint: Number of Patients with Dose Limiting Toxicity
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-center, single-arm, open-label phase I clinical study to determine the safety and efficacy of relapsed or refractory multiple myeloma subjects

Detailed Description

This study will recruit multiple myeloma subjects,and Subjects should undergo FC chemotherapy before returning the cells, then followed by infusion of YTS104 cells injection. YTS104 cells injection will be intravenously infused with a escalated dose of 1E6#3E6#6E6#1E7 cells/kg.

Registry

clinicaltrials.gov

Start Date

June 28, 2023

End Date

December 30, 2025

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Aged 18-75 years, gender is not limited;
•Patients diagnosed as relapsed/refractory multiple myeloma according to the International Myeloma Working Group (IMWG 2014) criteria for multiple myeloma after at least 3 lines of treatment (including at least one proteasome inhibitor and an immunomodulator based chemotherapy regimen), and at least one complete treatment cycle per line of treatment; Documented disease progression during or within 12 months after the most recent antimyeloma therapy (not limited to 12 months after CAR-T therapy as the last line of therapy);
•The presence of one or more measurable lesions at screening was defined as any of the following: 1) serum M-protein ≥0.5g/dL (≥5g/L), 2) urinary M-protein level ≥200 mg/24 hours; 3) serum free light chain (sFLC) ≥100 mg/L and serum κ/λ free light chain ratio abnormal (\<0.26 or \>1.65);
•Good organ function;
•ECOG score ≤1;
•The predicted survival time was ≥12 weeks;
•Female subjects of childbearing age or male subjects with partners of women of childbearing age agreed to use effective methods of contraception throughout the trial and for 12 months after cell infusion;
•The subjects voluntarily participated in the study, signed the informed consent form, and complied with the follow-up.

Exclusion Criteria

•A history of allergy to any component of the cell product;
•Patients who had used CAR-T cell therapy or any other gene transduction or other therapeutic products within 3 months after signing the informed consent, except those with undetectable CAR-T cells or CAR-T cells below the lower limit of detection;
•Subjects had plasma cell leukemia, Waldenström's macroglobulinaemia, POEMS syndrome, or primary light chain amyloidosis;
•Patients with a history of any of the following cardiovascular and cerebrovascular diseases within the preceding 6 months were screened;
•Congestive heart failure (New York Heart Association \[NYHA\]≥III), congenital long QT syndrome, left front half block (double bundle block), asymptomatic right bundle branch block allowed; Myocardial infarction, unstable angina pectoris, coronary angioplasty, stent implantation, coronary/peripheral artery bypass grafting;
•Cerebrovascular accident (CVA) and transient ischemic attack (TIA);
•Severe arrhythmias requiring treatment (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, etc.); d: Subjects had uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy;
•Pulmonary embolism, or deep venous thrombosis of the lower extremity requiring anticoagulation, or active lung disease and/or pneumonia have occurred within 6 months prior to screening;
•Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) and HBV DNA in peripheral blood were positive. Hepatitis C virus (HCV) antibody positive and HCV RNA positive; Treponema pallidum antibody was positive;
•Patients with known systemic lupus erythematosus, co-active or uncontrolled autoimmune diseases (e.g., Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.), primary or secondary immunodeficiency (e.g., HIV infection or severe infectious diseases);

Arms & Interventions

YTS104 cells injection

Subjects will receive cell infusion, with the initial cell dose of 1E6/kg. 1-6 subjects will be enrolled. The second dose group was 3E6 cells /kg with 1-6 subjects; The third and fourth dose groups were 6E6 cells /kg and 1E7 cells /kg, respectively, with 3-6 subjects.Subjects may undergo secondary or multiple retransfusion

Intervention: YTS104 Cells injection

Outcomes

Primary Outcomes

Number of Patients with Dose Limiting Toxicity

Time Frame: Within 28 days after cell transfusion

Dose-limiting toxicity was defined as adverse events associated with YTS104-cell injection within 28 days of cell transfusion, including grade 4 or 5 CRS and ICANS; grade 4 haematological adverse events did not return to grade 2 or baseline within 28 days of cell transfusion

Incidence and severity of adverse events

Time Frame: 24 months

After YTS104-cell infusion, adverse events will be graded as CTCAE 5.0