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

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

Overview

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.

Interventions

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

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Up to 28 years after Treatment]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after Treatment]

Secondary outcome measures (4)

• Overall response rate ,ORR [Time frame: Up to 12 weeks after CAR-T infusion]
• Duration of remission ,DOR [Time frame: Up to 1 years after CAR-T infusion]
• Event-free survival, EFS [Time frame: Up to 1 years after CAR-T infusion]
• Overall survival, OS [Time frame: Up to 1 years after CAR-T infusion]

Eligibility criteria

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):

• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration is less than 12 months;
• Ineffectively after first or multiple remedial treatments;
• 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):

• No response or relapse after second-line or above chemotherapy regimens;
• Primary drug resistance;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The first affiliated hospital of medical college of zhejiang university — Hangzhou

Identifiers

NCT: NCT06346912 · TXB2023022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗