A Phase 1 clinical trial to evaluate the safety and early efficacy of Chimeric Antigen Receptor T-cell (CAR T-cell) with IL-7Rα signaling targeting CD19 in children with relapsed and refractory B-cell Acute Lymphoblastic Leukemia (ALL) after complete standard treatments.

Hematological cancers are a significant public health problem in Thailand. Currently, treatment outcomes for patients with B-cell leukemia using standard chemotherapy regimens show satisfactory disease control and survival rates. However, patients with relapsed or refractory disease have very limited treatment options, as the chance of achieving remission through chemotherapy or targeted therapies before bone marrow transplantation is less than 20%. Once patients experience relapse or become refractory to treatment, their chance of surviving more than one year is extremely low. Therefore, developing new treatments for relapsed or refractory B-cell leukemia is urgently needed to provide additional treatment options, increase response rates, and improve survival outcomes in these patients.

Phase 1 to Phase 3 clinical research studies worldwide have demonstrated that treating patients with relapsed or refractory B-cell leukemia using the patients' own genetically modified T cells that specifically target B-cell leukemia and lymphoma cells can control the disease in 70-90% of B-cell leukemia patients. Approximately 50-60% of patients survive without disease recurrence for more than one year after treatment, with manageable side effects.

For these reasons, this research project aims to study the safety of treating Thai pediatric patients with relapsed or refractory B-cell leukemia using the patients' own T cells that have been genetically modified to become chimeric antigen receptor T cells specifically targeting proteins on the surface of leukemia cells. This research is being conducted for the first time in Thai pediatric patients. The research team expects this treatment to be highly safe and effective in controlling B-cell leukemia.

Inclusion Criteria:

1. Participants must have relapsed, or refractory ALL treated with at least one lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen.

   - Participant with Philadelphia Chromosome positive ALL are eligible if the progressed, had stable disease or relapsed after one line of therapy including tyrosine kinase inhibitors (TKIs)

2. The participant's disease must be CD19 positive either by immunohistochemistry or flow cytometry analysis

3. Age 1 - 18 years

4. Sex: Male or Female

5. Performance status: Lansky or Karnofsky score greater than or equal to 50

6. Normal organ function:

   • AST (SGOT) less 5 times the upper limit of normal (ULN)
   • ALT (SGPT) less 5 times the upper limit of normal (ULN)
   • Total bilirubin less 3 times the upper limit of normal (ULN)
   • Creatinine less 5 times the upper limit of normal (ULN)
   • SpO2 room air greater than or equal to 90%

7. Prior therapy wash-out before planned leukapheresis 7.1 Greater than or equal to 7 days post last chemotherapy/biologic therapy administration 7.2 Three half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy 7.3 At least 30 days from most recent cellular infusion 7.4 All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum of 0.5 mg/day dose of methylprednisolone. Corticosteroid physiologic replacement therapy is allowed

8. Participants and/or care givers must have the ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

1. Active GVHD that required systemic immunosuppressant with 4 weeks of enrollment
2. History of active malignancy other than non-melanoma skin cancer and carcinoma in situ (e.g. cervix, bladder, breast).
3. Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, Graft Versus Host Disease or psychiatric illness/social situations that would limit compliance with study requirements.
4. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with potential for teratogenic or abortifacient effect. Women of child bearing potential must have negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of mother with CAR-T cells, breast feeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving CAR-T cell infusion.
5. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
6. Serologic status reflecting active HIV, hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.
7. Participants who have a history of anaphylactic reaction to albumin.