CD19-BAFF CAR-T Cells Therapy for Patients With Relapsed / Refractory B-cell ALL and B-cell NHL

Non-hodgkin Lymphoma,B Cell Clinical Trial

Official title:

A Study of CD19-BAFF CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell ALL and B-cell NHL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06346912
• Other study ID #: TXB2023022
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 30, 2024
• Est. completion date: May 30, 2027

Study information

• Verified date: December 2023
• Source: Zhejiang University
• Contact: He Huang, MD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Clinical Trial for the safety and efficacy of CD19-BAFF CAR-T cells therapy for refractory/relapsed B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.

Description:

In this study, 20 patients with relapsed refractory B-cell ALL and B-cell NHL were proposed to undergo CD19-BAFF CAR-T cell therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19-BAFF CAR-T cell therapy for relapsed refractory B-cell ALL and B-cell NHL; At the same time, on the basis of expanding the sample size, more safety data on CD19-BAFF CAR-T cell treatment for relapsed refractory B-cell ALL and B-cell NHL were accumulated, including rare and delayed complications.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 30, 2027
• Est. primary completion date: May 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Gender unlimited,18< Age;
• 2. Patients diagnosed with B-cell acute lymphoblastic leukemia through histological or immunophenotyping tests; The clear diagnosis of B-cell non Hodgkin's lymphoma by cellular or histopathological examination mainly includes diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma
• 3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

1. CR not achieved after standardized chemotherapy;

2. CR achieved following the first induction, but CR duration is less than 12 months;

3. Ineffectively after first or multiple remedial treatments;

4. 2 or more relapses;

• 4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (by morphology), and/or >1% (by flow cytometry);
• 5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
• 6. Relapsed or refractory B-NHL (meeting one of the following conditions):

1. No response or relapse after second-line or above chemotherapy regimens;

2. Primary drug resistance;

3. Relapse after auto-HSCT;

• 7. At least one assessable tumor lesion per Lugano 2014 criteria;
• 8. Total bilirubin = 51 umol/L, ALT and AST = 3 times of upper limit of normal, creatinine = 176.8 umol/L;
• 9. Echocardiogram shows left ventricular ejection fraction (LVEF) = 50%;
• 10. No active infection in the lungs, blood oxygen saturation in indoor air is = 92%;
• 11. Estimated survival time = 3 months;
• 12. ECOG performance status 0 to 2;
• 13. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

• 1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
• 2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• 3. Pregnant/lactating women, or male or female patients with fertility who are unwilling to take effective contraceptive measures during the study period or at least 6 months after the last cell infusion
• 4. Patients with HIV infection;
• 5. Active infection of hepatitis B virus or hepatitis C virus;
• 6. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• 7. Other uncontrolled diseases that were not suitable for this trial;
• 8. Individuals who have received CAR-T therapy, CAR-NK therapy, or any other gene modified cell therapy product within 6 months;
• 9. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Related Conditions & MeSH terms

• Leukemia, B-Cell
• Lymphoma, B-Cell
• Non-hodgkin Lymphoma,B Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CD19-BAFF Targeted CAR T-cells
Each subject receive CD19-BAFF Targeted CAR T-cells by intravenous infusion

Locations

Country	Name	City	State
China	The first affiliated hospital of medical college of zhejiang university	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Shanghai YaKe Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 28 years after Treatment
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after Treatment
Secondary	Overall response rate ,ORR	The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response).	Up to 12 weeks after CAR-T infusion
Secondary	Duration of remission ,DOR	The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion	Up to 1 years after CAR-T infusion
Secondary	Event-free survival, EFS	The time from first achieving CR/CRi to relapse or death	Up to 1 years after CAR-T infusion
Secondary	Overall survival, OS	The time from CAR-T infusion to death due to any cause	Up to 1 years after CAR-T infusion