Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia

A Clinical Study on the Safety and Effectiveness of Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia

A Clinical Study on the Safety and Effectiveness of donor derived CD19 CAR-T Cells in the treatment of R/R B-cell acute lymphoblastic leukemia

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells injection

Detailed Description

In this study, 15 patients with relapsed refractory B-cell acute lymphoblastic leukemia were proposed to undergo CD19 CAR-T Cells therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19 CAR-T Cells therapy for relapsed refractory B-cell acute lymphoblastic leukemia; At the same time, on the basis of expanding the sample size, more safety data on CD19 CAR-T Cells treatment for relapsed refractory B-cell acute lymphoblastic leukemia were accumulated.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, MD; Phone Number: 0571-87233772; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, MD; Phone Number: 0571-87233772; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: He Huang, MD; Phone Number: 0571-87233772; Email: hehuangyu@126.com
      • Contact: Yongxian Hu, MD; Phone Number: 0571-87233772; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Age ≥18 years old, gender unlimited;
• 2. Abnormal B cell immunotyping was CD19 positive;
• 3. Patients diagnosed with B-cell acute lymphoblastic leukemia by histological or immunotyping;

• 4. Meets the diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and includes any of the following conditions:

  1. No CR was obtained after standard chemotherapy;
  2. CR was induced for the first time, but the duration of CR was less than 12 months;
  3. R/R B-ALL that does not work after the first or more remedial treatments;
  4. Two or more relapses;
• 5. The researchers believed that the patient had been adequately treated, such as auto-HSCT, auto-CART could not be prepared or preparation failed. Autologous CAR-T preparation failure was defined as including too few autologous lymphocytes (<1×109) or insufficient expansion during preparation or failure to meet the release criteria;
• 6. Total bilirubin ≤51 ( μmol/L), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal, creatinine ≤176.8 (μmol/L);
• 7. Absolute neutrophil count: ≥ 0.5×109/L; Platelet: ≥ 30×109/L; Hemoglobin ≧60g/L;
• 8. Echocardiography showed left ventricular ejection fraction (LVEF) ≥40%;
• 9. The estimated survival is more than 3 months;
• 10. ECOG score 0-2;
• 11. Women and men who are fertile must consent to the use of appropriate contraception before entering the study, during study participation, and for 6 months after transfusion (the safety of this therapy for the unborn child is not known, with unknown risks);
• 12. Subjects who are willing to participate in the study are able to understand and have the ability to sign informed consent.

Exclusion Criteria:

• 1. Known allergies to research preconditioning measures, etc;
• 2. People with a history of epilepsy or other central nervous system disorders;
• 3. People with a history of prolonged QT or severe heart disease;
• 4. Less than 100 days after receiving allogeneic hematopoietic stem cell transplantation;
• 5. Hiv-infected person;
• 6. Persons with active hepatitis B or C virus; Those who are not cured have active infections;
• 7. Insufficient amplification ability (< 5x) in response to CD3 / CD28 costimulatory signals;
• 8. Combined use of systemic steroids (e.g., prednisone ≥20mg) within 3 days prior to screening, except for ongoing or intermittent use of topical, inhaled or intranasal steroids within 2 weeks or at present; Or have systemic diseases that require long-term use of immunological agents;
• 9. Patients who received anti-cancer chemotherapy or other drugs within 2 weeks prior to screening;
• 10. Any situation that the investigator believes may increase the risk of the subjects or interfere with the study results.

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 B-cell Acute Lymphoblastic Leukemia 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 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells injection; Each subject receive CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells by intravenous infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall survival, OS	After transplantation until death from any cause.	Up to 2 years after Treatment
Event-free survival (EFS)	defined as the time from the date of receiving the infusion to the date of treatment failure (failure to achieve CR/CRh/CRi/MLFS/PR after both efficacy assessments), or relapse (hematologic relapse or extramedullary relapse after CR/CRh/CRi), or death from any cause, whichever occurs first. When an EFS event was "Ineffective Therapy", the primary analysis of EFS was performed on a 1-day basis (ie, time to treatment received as the event). For a more comprehensive assessment, sensitivity analyses could be performed using the actual date of treatment failure, end of treatment, or start of next-line anti-leukemia therapy as the end of EFS for treatment failure, respectively.	Up to 1 years after CAR-T infusion

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CD19 CAR-T
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: TXB2024011

Drug and device information, study documents

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