Clinical trial NCT06346912: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Lymphoblastic Leukemia,B-Cell
Non-hodgkin Lymphoma,B Cell
Keywords: CD19-BAFF CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2024-04-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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):

  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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 years after Treatment
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after Treatment
Secondary outcomes:
measure: Overall response rate ,ORR
timeFrame: Up to 12 weeks after CAR-T infusion
measure: Duration of remission ,DOR
timeFrame: Up to 1 years after CAR-T infusion
measure: Event-free survival, EFS
timeFrame: Up to 1 years after CAR-T infusion
measure: Overall survival, OS
timeFrame: Up to 1 years after CAR-T infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: