CD19 & CD20 Bispecific CAR T Cells for Relapsed / Refractory B Cell Hematological Tumors

Phase 1

Recruiting

• Conditions: B-Cell Lymphoblastic Leukemia/Lymphoma
• Interventions: Drug: CD19&CD20 bispecific CAR-T cells

• Registration Number: NCT06503094
• 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 \& CD20 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 \& CD20 is designed with a 4-1BB costimulatory domain and an antigenic recognition region with a tandem structural sequence to recognize CD20 or CD19 by a single structure. CD19 \& CD20 bispecific CAR-T cells can identify CD 19 or CD 20 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 CD20 positive).

Study Timeline

• Study Start: 2024-01-14
• Study First Submitted: 2024-06-17
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-09
• Last Update Submitted: 2024-07-09
• Study First Posted: 2024-07-16
• Last Update Posted: 2024-07-16
• Primary Completion: 2025-12-18
• Study Completion: 2026-06-18

Recruitment & Eligibility

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

Inclusion Criteria

• Fully understand and voluntarily sign the informed consent form, and be willing and able to comply with the visit, treatment protocol, laboratory tests, and other study requirements specified in the flow sheet;

• CD 19 + / CD 20 + 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.

• B-cell hematological tumors include the following 3 categories:

  1. B-cell acute lymphoblastic leukemia (B-ALL);
  2. Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL);
  3. Invasive B-cell lymphoma (DLBCL, BL, and MCL);

• With measurable or evaluable lesions: Lymphoma patients require a single lesion 15mm or 2 or more lesions 10mm; patients with leukemia require persistent positive or positive recurrence of bone marrow MRD.

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

• The results of FCM or immunohistochemical detection of tumor antigen (CD 19 / CD 20) were positive.

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

Exclusion Criteria

• Appearance of one of the following cardiac criteria: atrial fibrillation; myocardial infarction in the last 12 months; prolonged QT syndrome or secondary QT extension, as judged by the investigator. Echocardiography LVSF <30% or LVEF <50%; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV (confirmed by echocardiography within 12 months of treatment).
• Active GVHD.
• History of severe pulmonary function impairment disease.
• Other malignant tumors in the advanced stage.
• Severe infection or persistent infection that cannot be effectively controlled.
• Combined with severe autoimmune disease or innate immune deficiency.
• 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).
• Human immunodeficiency virus (HIV) infection or syphilis infection.
• History of severe allergies to biological products (including antibiotics).
• There are central nervous system disorders, such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, etc..
• Female patients are in pregnancy and lactation, or have a pregnancy plan within 12 months.
• situations where the investigator may increase the risk or interfere with the test results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Effective of CD19&CD20 bispecific CAR-T cells	CD19&CD20 bispecific CAR-T cells	The infusion dose range of cells in this trial is recommended: 2 to 6 10\^6 And CAR-T cells / kg.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-related Adverse Events	within 3 years after infusion	Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Partial response rate (PR) of administering CD19&CD20 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors	within 3 year after infusion	PR will be assessed from CAR-T cell infusion to death or last follow-up.
Overall response rate (ORR) of administering CD19&CD20 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&CD20 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).

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS) of administering CD19&CD20 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).
Progress-free survival (PFS) of administering CD19&CD20 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).
Event-free survival (EFS) of administering CD19&CD20 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors	within 3 years after infusion	EFS will be assessed from CAR-T cell infusion to death or last follow-up (censored).

Trial Locations

Locations (1)

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