About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
The participant's disease must be CD19 positive either by immunohistochemistry or flow cytometry analysis
Age 1 - 18 years
Sex: Male or Female
Disqualifiers
Active GVHD that required systemic immunosuppressant with 4 weeks of enrollment
History of active malignancy other than non-melanoma skin cancer and carcinoma in situ (e.g. cervix, bladder, breast).
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.
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.
Trial design
Single group
Treatments tested in this trial
CD19-IL7Ra CAR-T cells
Biological/VaccineAutologous T cells lentiviral transduced to express a CD19-specific chimeric antigen receptor (CAR) with the addition of an IL-7 receptor alpha signaling domain, administered via central venous access catheter after lymphodepletion
Treatment groups
Trial outcomes
Primary outcomes
Incidence and Severity of Adverse Events of CD19-IL7Ra CAR T-cells infusion in B-cell acute lymphoblastic leukemia patients.
The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
Secondary outcomes
The overall response rate of B-cell acute lymphoblastic leukemia
The overall response rate will be assessed using standard response criteria for acute lymphoblastic leukemia patients through a combination of clinical, hematologic, and molecular assessments. The response categories are Minimal Residual Disease (MRD), Complete Response (CR), Complete Response with Incomplete Count Recovery (CRi), Stable Disease (SD), and Progressive Disease (PD).
Other outcomes
Persistence of anti-CD19 CAR-T cell in peripheral blood
Persistence of anti-CD19 CAR-T cell in peripheral blood of leukemia patients measuring by flow cytometry and qPCR.
Serum cytokine level measurement
Serum cytokine level measurement including IL-2,IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma before and after CD19-IL7Ra CAR T-cell infusion
Sponsors and contacts
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Chulalongkorn University
Lead sponsor
King Chulalongkorn Memorial Hospital
Collaborator