CD19 & CD22 Bispecific CAR T Cells in the Treatment of Relapsed/Refractory B Cell Hematologic Tumors

Phase 1

Recruiting

• Conditions: B-Cell Lymphoblastic Leukemia/Lymphoma
• Interventions: Drug: CD19&CD22 bispecific CAR-T cells

• Registration Number: NCT06735495
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

This study is a multi-center, open, prospective single-arm clinical study of patients with relapsed / refractory B cell hematological tumors to evaluate the safety and efficacy of CD19 \& CD22 bispecific CAR-T cells in relapsed / refractory B cell hematological tumors while collecting pharmacokinetics and pharmacodynamics indicators of CAR-T cells.

Detailed Description

Since 2010, CAR-T ( chimeric antigen receptor T cell) therapy has shown good results in tumor treatment and has achieved positive clinical therapeutic effects in hematological tumors. The structure of the dual-target CAR-T of CD19 \& CD22 is designed with a 4-1BB costimulatory domain and an antigenic recognition region with a tandem structural sequence to recognize CD22 or CD19 by a single structure. CD19 \& CD22 bispecific CAR-T cells can identify CD 19 or CD 22 with the advantage that the single target CAR-T does not have, reducing the possibility of target loss. The structure has been optimized to enhance the safety to treat B cell-derived hematological tumors (at least CD19 positive or CD22 positive).

Study Timeline

• Study Start: 2024-11-04
• Status Verified: 2024-12
• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-10
• Last Update Submitted: 2024-12-10
• Study First Posted: 2024-12-16
• Last Update Posted: 2024-12-16
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1.CD 19 + / CD 22 + B cell hematological tumor was confirmed by pathological and histological examination, and the patient met the following criteria for relapsed or refractory B cell hematological tumor:

1. Refractory / relapsed B lymphocytic leukemia (1 of the following 4 items can be met):

   i . Recurrence within 6 months of first remission; ii. Primary refractory without complete remission after 2 cycles of standard chemotherapy regimen; iii. No complete remission or recurrence after first-line or multiline salvage chemotherapy; iv. Not eligible for HSCT conditions, abandonment of HSCT, or relapse after HSCT due to conditional limitations.

2. Refractory / relapsed B-cell lymphoma (meet the following item 1 of the first 4 items plus item 5):

i . After four courses of chemotherapy with a standard regimen, tumor shrinkage was less than 50% or disease progression; ii . CR after standard regimen chemotherapy, but relapsed within 6 months; iii.2 or more recurrences after CR; iv . Not suitable for hematopoietic stem cell transplantation, or abandoning HSCT due to conditional restrictions or relapse after hematopoietic stem cell transplantation; v . Subject must have received prior adequate treatment, including at least: a monoclonal antibody against CD 20 and combination chemotherapy containing an anthracycline drug agent.

2.The results of FCM or immunohistochemical detection of tumor antigen (CD 19 / CD 22) were positive.

3.The estimated survival period is more than 3 months starting from the signing of the informed consent form.

4.Good organ function,Meet the following requirements：

1. HGB≥70g/L(transfusible)
2. Liver and kidney function: creatinine ≤1.5XULN: total bilirubin ≤1.5XULN:ALT and AST≤2.5X ULN
3. Cardiopulmonary function: left ventricular ejection fraction >50%; Blood oxygen saturation >90%;

5.Subjects with the Eastern Cooperative Oncology Group (ECOG) fitness scores of 0 to 2.

Exclusion Criteria：(If meet any of the following criteria, patients will not be included)

1. Serious heart insufficiency,LVEF <50%
2. History of severe pulmonary function impairment disease.
3. Other malignant tumors in the advanced stage.
4. Severe infection or persistent infection that cannot be effectively controlled.
5. Combined with severe autoimmune disease or innate immune deficiency.
6. Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA 500 IU / ml and abnormal liver function] or hepatitis C antibody [HCV-Ab] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function).
7. Human immunodeficiency virus (HIV) infection or syphilis infection.
8. History of severe allergies to biological products (including antibiotics).
9. Acute graft-versus-host response (GVHD) allogeneic hematopoietic stem remained one month after immunosuppressant discontinuation.
10. Patients who have other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participating in the clinical trial or interfere with the study results, and who are deemed unsuitable for participation in the clinical trial by the investigator

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Effective of CD19&CD22 bispecific CAR-T cells	CD19&CD22 bispecific CAR-T cells	The infusion dose range of cells in this trial is recommended: 1 to 2 10\^6 And CAR-T cells / kg.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Complete response rate (CR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Complete response with incomplete blood recovery rate (CRi) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	CRi will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Partial response rate (PR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	PR will be assessed from CAR-T cell infusion to death or last follow-up.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	DOS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Progress-free survival (PFS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	PFS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Overall survival (OS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	OS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
The Peripheral blood vector copy number of patients of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies	within 3 years after infusion	Quantity of CD19\&CD22 CAR copies in peripheral blood will be determined by using flow cytometry and quantitative polymerase chain reaction.
The Cmax of CAR T cells of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies	within 3 years after infusion	The highest concentration of CAR T cells amplified in peripheral blood (Cmax) during the treatment of relapsed/refractory B-cell hematological malignancies
The Tmax of CAR T cells of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies	within 3 years after infusion	Time to maximum concentration of CAR T cells in peripheral blood (Tmax) during the treatment of relapsed/refractory B-cell hematological malignancies
The AUC28D of CAR T cells of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies	within 3 years after infusion	Area under the curve of peripheral blood CAR T cells at 28 days in peripheral blood (AUC28D) during the treatment of relapsed/refractory B-cell hematological malignancies

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China