Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors, Hematologic Disease
Conditions
Keywords
cell therapy, hematological tumors
Brief summary
This clinical trial aims to evaluate the efficacy and safety of CAR-T cell therapy in patients with relapsed/refractory hematologic malignancies.
Detailed description
This clinical trial aims to evaluate the efficacy and safety of CAR-T cell therapy in patients with relapsed/refractory hematologic malignancies. The primary objective is to determine the maximum tolerated dose (MTD), safety profile, and the overall response rate (ORR) of CAR-T cells in these patients. Secondary objectives include assessing marrow remission rates and minimal residual disease (MRD) clearance at various time points (2 weeks, 1 month, 3 months, 6 months, and 1 year) in patients with bone marrow involvement, as well as evaluating the changes in multiple sites of involvement through PET-CT or PET-MRI before and one year after CAR-T therapy. The study will also track event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) rates at 1, 2, 3, and 5 years post-treatment.
Interventions
DRUGCellular Therapy
This intervention involves the infusion of autologous or allogeneic CAR-T cells into patients with relapsed/refractory hematologic malignancies. CAR-T cells are modified to target specific antigens on the surface of cancerous cells. After the infusion, patients will be monitored for response and safety. Administration: Intravenous infusion. Dosage: The maximum tolerated dose (MTD) will be determined as part of the study, with dose escalation used to identify the optimal and safest dose of CAR-T cells for treatment.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients with relapsed/refractory hematologic malignancies confirmed to express CD19, CD22, CD20, CD7, CD5, CD2, CD79b, BCMA, GPCR5D, CD38, CD33, CD123, CD133, CLL1, EBV (GP350, LMP1), CMV (Gb21, gB280…) or other validated targets (supported by domestic and international preclinical/clinical evidence) who meet the following criteria: Male or female, aged ≥18 years and \<75 years; Newly diagnosed patients with refractory disease (as defined by respective diagnostic criteria) after chemotherapy; Newly diagnosed patients with disease progression during chemotherapy and poor anticipated response to further chemotherapy; Patients with relapsed disease (≥1 recurrence) and confirmed residual tumor evidence; Patients with relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT); Patients with relapse after CAR-T therapy; Patients with hematologic malignancies deemed incurable by current surgical, radiotherapy, or chemotherapy interventions.
Exclusion criteria
Patients meeting any of the following criteria will be excluded: Life expectancy \<12 weeks; Genetic testing reveals mutations or structural variants associated with the target antigens; Severe graft-versus-host disease (GVHD) requiring immunosuppressive therapy in post-HSCT relapse patients; Post-HSCT relapse \<3 months with no available donor; Organ dysfunction: Serum creatinine \>2.5 mg/dL; ALT/AST \>5× upper limit of normal (ULN); Total bilirubin \>2 mg/dL; Uncontrolled active infection; Active hepatitis B/C or HIV infection; Anticipated early loss to follow-up (\<3 months post-treatment); Failure to provide signed informed consent or lack of ethics committee approval; Concurrent systemic conditions that may interfere with study participation; Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adverse events. | 1 month | Type, incidence and severity of adverse events |
| Maximum tolerated dose | 1 month | The maximum dose that does not cause death of the subject |
| Overall response rate | 3 months | ORR in patients is defined as the rate of complete remission (CR, CRh) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall incidence and severity of adverse events. | 12 months | Overall incidence and severity of adverse events will measure in this trial. |
| Rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR | 12 months | The rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR in D28; 3,6,12months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Level of circulating CAR T cells | 12 months | To investigate the relationship between the dynamic changes of CAR-T cells in the peripheral blood and treatment outcomes, as detected by FCM and/or real-time quantitative PCR technology |
Countries
China
Outcome results
None listed