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

Early Phase 1

Recruiting

• Conditions: Non-hodgkin Lymphoma,B Cell; Acute Lymphoblastic Leukemia,B-Cell
• Interventions: Biological: CD19-BAFF Targeted CAR T-cells

• Registration Number: NCT06346912
• Lead Sponsor: Zhejiang University

Brief 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.

Detailed 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.

Study Timeline

• Status Verified: 2023-12
• Study First Submitted: 2024-03-29
• Study First Submitted QC: 2024-04-03
• Study First Posted: 2024-04-04
• Last Update Submitted: 2024-05-13
• Last Update Posted: 2024-05-14
• Study Start: 2024-05-30
• Primary Completion: 2027-05-30
• Study Completion: 2027-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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):

  4. CR not achieved after standardized chemotherapy;

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

  6. Ineffectively after first or multiple remedial treatments;

  7. 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):

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

  8. Primary drug resistance;

  9. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of CD19-BAFF Targeted CAR T-cells	CD19-BAFF Targeted CAR T-cells	Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	Up to 28 years after Treatment	Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years after Treatment	Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary Outcome Measures

Name	Time	Method
Duration of remission ,DOR	Up to 1 years after CAR-T infusion	The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion
Overall response rate ,ORR	Up to 12 weeks after CAR-T infusion	The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response).
Overall survival, OS	Up to 1 years after CAR-T infusion	The time from CAR-T infusion to death due to any cause
Event-free survival, EFS	Up to 1 years after CAR-T infusion	The time from first achieving CR/CRi to relapse or death

Trial Locations

Locations (1)

The first affiliated hospital of medical college of zhejiang university; 🇨🇳 Hangzhou, Zhejiang, China