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

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 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.

Study Overview

• Status: Recruiting
• Conditions: Non-hodgkin Lymphoma,B Cell; Acute Lymphoblastic Leukemia,B-Cell
• Intervention / Treatment: Biological: CD19-BAFF Targeted CAR T-cells

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yongxian Hu, MD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com
• Study Contact Backup: Name: He Huang, MD; Phone Number: 86-13605714822; Email: hehuangyu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com
      • Contact: He Huang, MD; Phone Number: 86-13605714822; Email: hehuangyu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of 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.	Biological: CD19-BAFF Targeted CAR T-cells; Each subject receive CD19-BAFF Targeted CAR T-cells by intravenous infusion; Other Names: CD19-BAFF Targeted CAR T-cells injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival, EFS	The time from first achieving CR/CRi to relapse or death	Up to 1 years after CAR-T infusion
Overall survival, OS	The time from CAR-T infusion to death due to any cause	Up to 1 years after CAR-T infusion
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
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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Shanghai YaKe Biotechnology Ltd.
• Investigators: Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: March 29, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: CD19-BAFF CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, B-Cell
• Other Study ID Numbers: TXB2023022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No