Clinical trial NCT05613348: CD19 CAR T-cell Target Relapsed/Refractory Acute B Cell Leukemia/Lymphoma
Official title: Humanized CAR19T2 T Cell in Children With Refractory/Relapsed B-cell Leukemia/Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
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
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: Guangdong Zhaotai Cell Bio-tech Co., LTD
First posted: 2022-11-14
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: CD19 CAR-T cells treating B-cell hematological malignancies have achieved unprecedented success. In this study, we investigated new third-generation autologous T cells (CAR19T2 T cells) genetically modified with humanized anti-CD19 construct incorporating CD28 and Toll-like receptor 2 (TLR2) costimulatory domains. CAR19T2 T cells will be modified before the infusion to those which could identify and kill the tumor cells (CD19+ cells). 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.

Eligibility criteria: Inclusion Criteria:

1. ≥1 year old and ≤18 years.
2. Patients with relapsed and/or refractory CD19-positive B-cell acute leukemia/lymphoma.
3. 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.
4. 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.
5. Adequate vascular access leukapheresis procedure. Absolute Lymphocyte count (ALC) greater than or equal to 100 cells/μL.
6. 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.
7. Life expectancy of greater than or equal to 3 months.
8. Patients or legal guardians must sign an informed consent.

Exclusion Criteria:

1. Prior received any other CAR T cell and tumor vaccine treatment.
2. Patient with a previous history of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
3. Patient with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
4. Acute GVHD grade II-IV (Glucksberg criteria) or chronic GVHD requiring systemic treatment within 4 weeks before enrollment.
5. 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)
6. Severe psychological disorder or psychiatric illness.
7. Combined with life-threatening severe organ failure.
8. Major non-medicinal surgery within four weeks.
9. Received other clinical trials within four weeks. 10. Women who are pregnant or breastfeeding.

11. 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.
* Receive blinatumomab within 4 weeks, inotuzumab ozogamicin, and rituximab within 4 months, and alemtuzumab within 6 months before collection.

  12. Tyrosine Kinase Inhibitor within 1 week and asparaginase within 4 weeks prior to CAR T-cell infusion.

  13. In the opinion of the PI, patients are present for any condition, not for enrollment.

Primary outcomes:
measure: Overall response rate
timeFrame: 3 months
measure: The maximum tolerated dose(MTD) of CAR19T2 T cells
timeFrame: 24 weeks
measure: Adverse Events (AEs)
timeFrame: 3 years
Secondary outcomes:
measure: Minimal residual disease (MRD) negative response rate
timeFrame: Up to 12 months after infusion
measure: Event-free survival (EFS)
timeFrame: Up to 3 years after infusion
measure: Overall survival (OS)
timeFrame: Up to 3 years after infusion
measure: CAR-T cell expansion level
timeFrame: 24 months
measure: The duration of CAR T cell persistence
timeFrame: 24 months
measure: Rate of hematopoietic stem cell transplant (HSCT) after CAR19T2 T cell infusion
timeFrame: Up to 3 years after CAR19T2 T infusion
measure: Maximum concentration of CAR19T2 T cell and cytokines.
timeFrame: 12 months
measure: Time to peak concentration of CAR19T2 T cell and cytokines.
timeFrame: 12 months
measure: Area under the curve of CAR19T2 T cell and cytokines.
timeFrame: 12 months
measure: Incidence of hypogammaglobulinaemia
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Zhaotai Cell Bio-tech Co., LTD
state: Guangdong
city: Guanzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
Study officials:
affiliation: Zhujiang Hospital
name: Lihua Yang
role: PRINCIPAL_INVESTIGATOR
References: