Acute Lymphoblastic Leukemia, Pediatric, Lymphoma, B-Cell
Conditions
Keywords
CAR-T cell, Pediatric
Brief summary
This study seeks to examine the efficacy and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor (CAR) targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoma. The overall goal of this study is to validate the safety profile of administration CD19-CAR T cells and describe the response rate in children with relapsed/refractory ALL or lymphoma.
Interventions
BIOLOGICALCAR-T
CAR-T cell (CHXCART01) infusion intravenously once at a dose of 0.2-2 million cells/kg recipient body weight
Sponsors
Hong Kong Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have relapsed or refractory ALL or lymphoma treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen. * The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available. * Age 1-17 years. * Performance status: Subjects \> 10 years of age: Karnofsky ≥ 50%; Subjects ≤ 10 years of age: Lansky scale ≥ 50%. * Normal organ function. * Total bilirubin ≤ 3 times upper limit of normal * AST (SGOT) ≤ 5 times upper limit of normal * ALT (SGPT) ≤ 5 times upper limit of normal * Serum Creatinine ≤ 2 times upper limit of normal * Subjects must have the following hematologic function parameters: Hemoglobin (Hb) level \> 8 g/dL; Absolute Lymphocyte Count \> 0.1x10\^9/L; Platelet \> 50x10\^9/L * Prior therapy wash-out. At least 2 weeks or 5 half lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis. * Subjects' parent or legal guardian must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Autologous transplant within 6 weeks of planned CAR T cell infusion. * Recipient of CAR-T cell therapy outside of this protocol. * Active central nervous system (CNS) or meningeal involvement by tumor. * History of additional active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast). * Active human immunodeficiency virus (HIV) infection. * Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant or breastfeeding women. * Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy. * Serologic status reflecting active hepatitis B or C infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) for ALL and Overall response rate (ORR) for lymphoma | 1 month for subjects with ALL, and 3 months for subjects with lymphoma | Complete response for ALL was defined as leukemic cells \<5% in bone marrow. Overall response for lymphoma was defined as complete response plus partial response defined by Lugano criteria. |
| Incidence and severity of adverse events | through study completion, an average of 6 months | Severity of adverse events are graded according to CTCAEv5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of minimal residual disease for ALL | 1 month | Measurable residual disease in bone marrow by flow cytometry or PCR methods. |
| Overall survival | 1 year | survival as estimated by Kaplan-Meier method. Death from any cause is considered as event for analysis. |
| Event-free survival | 1 year | Event-free survival as estimated by Kaplan-Meier method. Events are death from any cause, or relapse or progression of underlying disease. |
| Proportion of products successfully manufactured | at the time of CAR-T cell infusion | Success defined as meeting product release criteria with at least 0.2 million cells/kg recipient body weight |
Countries
Hong Kong
Contacts
Primary ContactDaniel Cheuk, MBBS
Outcome results
None listed