Clinical trial NCT06849921: Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors
Official title: Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors
Hematologic Disease
Keywords: cell therapy
hematological tumors
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria deemed appropriate by the investigator.

Primary outcomes:
measure: adverse events.
timeFrame: 1 month
measure: Maximum tolerated dose
timeFrame: 1 month
measure: Overall response rate
timeFrame: 3 months
Secondary outcomes:
measure: Overall incidence and severity of adverse events.
timeFrame: 12 months
measure: Rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR
timeFrame: 12 months
Other outcomes:
measure: Level of circulating CAR T cells
timeFrame: 12 months
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
References: