CD19 CAR T-cell Target Relapsed/Refractory Acute B Cell Leukemia/Lymphoma

NCT05613348 | Withdrawn Phase 1

• 1 other identifier: 2022-KY-094
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to evaluate the safety and efficacy of humanized Anti-CD19 Chimeric Antigen Receptor-T cell (CAR19T2 T cell) in children with refractory/relapsed B-cell acute lymphoblastic leukemia/lymphoma.

Conditions

B-cell Acute Lymphoblastic Leukemia; B-Cell Lymphoma, Unspecified

Keywords

CAR T-cell; CAR19T2 T cell; refractory/relapsed B-cell acute lymphoblastic leukemia; refractory/relapsed Lymphoma

Outcome Measures

Primary Outcomes (3)

• Overall response rate

  A total number of patients achieved a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and three months by an independent review committee(IRC) assessment, as evaluated by peripheral blood, bone marrow, central nervous system (CNS) symptoms, physical exam (PE), and cerebrospinal fluid(CSF).

  3 months

• The maximum tolerated dose(MTD) of CAR19T2 T cells

  The maximum tolerated dose(MTD) of CD19-positive relapsed/ refractory acute leukemia/lymphoma treated with CAR19T2 T cells.

  24 weeks

• Adverse Events (AEs)

  Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups).

  3 years

Secondary Outcomes (10)

• Minimal residual disease (MRD) negative response rate

  Up to 12 months after infusion

• Event-free survival (EFS)

  Up to 3 years after infusion

• Overall survival (OS)

  Up to 3 years after infusion

• CAR-T cell expansion level

  24 months

• The duration of CAR T cell persistence

  24 months

Study Arms (1)

humanized CAR19T2 T cell to B-cell acute lymphoblastic leukemia/lymphoma

EXPERIMENTAL

Patients received fludarabine and cyclophosphamide (Flu/Cy) for lymphodepletion (Cy at 300-500 mg/m2/dose for four days and Flu at 20-30 mg/m2/dose for two days) before CAR19T2 T cells administration. This CAR19T2 T cell will be infused over 30 minutes on days Day 0.

Biological: CD19 CAR T-Cell(CAT19T2)

Interventions

CD19 CAR T-Cell(CAT19T2) BIOLOGICAL

Drug: Fludarabine， Administered intravenously Drug: Cyclophosphamide， Administered intravenously

humanized CAR19T2 T cell to B-cell acute lymphoblastic leukemia/lymphoma

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≥1 year old and ≤18 years.
• Patients with relapsed and/or refractory CD19-positive B-cell acute leukemia/lymphoma.
• Leukemia/lymphoma relapsed after allogeneic hematopoietic stem cell transplantation within four weeks, all immunosuppressive agents were stopped for at least four weeks, and no active graft-versus-host disease(GVHD) was detonated.
• Lansky play (≤16 years old) scale ≥60% or Karnofsky (\>16 years old) score ≥60% and Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory to assess the performance score.
• Adequate vascular access leukapheresis procedure. Absolute Lymphocyte count (ALC) greater than or equal to 100 cells/μL.
• Adequate renal, hepatic, pulmonary, and cardiac function is defined as the following:
• Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 5 upper limit of normal (ULN), Total bilirubin ≤2 x ULN.
• A serum creatinine based on age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL (both male and female);2 to \< 6 years: maximum serum creatinine 0.8 mg/dL (both male and female); 6 to \< 10 years: maximum serum creatinine 1 mg/dL (both male and female); 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL (both male and female); 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female); \>=16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female).
• Baseline oxygen saturation \> 92% on room air.
• Echocardiogram or left ventricular ejection fraction (LVEF) greater than or equal to 45% confirmed by echocardiogram, no evidence of pericardial effusion (except trace or physiological), and no clinically significant arrhythmias.
• Life expectancy of greater than or equal to 3 months.
• Patients or legal guardians must sign an informed consent.

You may not qualify if:

• Prior received any other CAR T cell and tumor vaccine treatment.
• Patient with a previous history of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• Patient with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
• Acute GVHD grade II-IV (Glucksberg criteria) or chronic GVHD requiring systemic treatment within 4 weeks before enrollment.
• History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc. (Except for CNS involvement of underlying hematological malignancy)
• Severe psychological disorder or psychiatric illness.
• Combined with life-threatening severe organ failure.
• Major non-medicinal surgery within four weeks.
• Received other clinical trials within four weeks. 10. Women who are pregnant or breastfeeding.
• \. The following drugs patients must be stopped prior to leukapheresis:
• Tyrosine Kinase Inhibitor (TKI) must be discontinued more than or equal to 3 days before collection.
• Salvage chemotherapy must be stopped \> 2 weeks and intrathecal chemotherapy in the 7 days prior to collection.
• Systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone in the 7 days before collection.
• Donor lymphocyte infusions (DLI) and Immunosuppressive therapies within 4 weeks before collection.
• Received clofarabine or cladribine within 3 months prior to collection.

Sponsors & Collaborators

• Zhujiang Hospital: lead
• Guangdong Zhaotai Cell Bio-tech Co., LTD: collaborator

Study Sites (2)

Guangdong Zhaotai Cell Bio-tech Co., LTD

Guangzhou, Guangdong, China

Location

Zhujiang Hospital of Southern Medical University

Guanzhou, Guangdong, China

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, B-Cell; Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lihua Yang

  Zhujiang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: November 14, 2022
• Study Start: December 1, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 18, 2024

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)