Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors

This clinical trial aims to evaluate the efficacy and safety of CAR-T cell therapy in patients with relapsed/refractory hematologic malignancies.

Study Overview

• Status: Active, not recruiting
• Conditions: Hematologic Disease; Precise Design of Cell Therapy for Relapsed and Refractory Hematological Tumors
• Intervention / Treatment: Drug: Cellular Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200020
      • Ruijin Hospital, Shanghai Jiaotong University School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Precise Design of CAR-cell Injection; The drug for this trial is Precise Designof CAR- cells transduced with the lentiviral vector . The dose is 2x10e6 ~1x10e7 CAR-cell/kg in patients with relapsed/refractory hematologic malignancies.

Drug: Cellular 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events.	Type, incidence and severity of adverse events	1 month
Maximum tolerated dose	The maximum dose that does not cause death of the subject	1 month
Overall response rate	ORR in patients is defined as the rate of complete remission (CR, CRh)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall incidence and severity of adverse events.	Overall incidence and severity of adverse events will measure in this trial.	12 months
Rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR	The rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR in D28; 3,6,12months.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of circulating CAR T cells	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	12 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: February 23, 2025
• First Submitted That Met QC Criteria: February 23, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 23, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: cell therapy; hematological tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Neoplasms; Hematologic Diseases
• Other Study ID Numbers: ruijinH-KY2024-394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No