CD19-directed CAR T cells with IL-7Rα signaling for children with relapsed or refractory B-cell ALL

Safety and Preliminary Efficacy of CD19 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell (CMD63) in Relapse and Refractory Pediatric B-cell Acute Lymphoblastic Leukemia

We will test whether a child's own T cells, changed to target CD19 and boost IL‑7 signaling, can safely treat children aged 1–18 with relapsed or refractory B-cell acute lymphoblastic leukemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 1 Year to 18 Years
• Sex: All
• Sponsor: Chulalongkorn University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, Chimeric Antigen Receptor
• Locations: 3 sites (Bangkok, Bangkoknoi and 2 other locations)
• Trial ID: NCT07078929 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, multi-center effort to use autologous T cells genetically modified to express a CD19-directed chimeric antigen receptor that includes IL-7Rα signaling for pediatric patients with relapsed or refractory B-cell ALL. Patients will have their T cells collected, engineered and expanded, and then reinfused with close monitoring for safety and early signs of anti-leukemia activity. The study focuses on safety endpoints and early efficacy signals in children treated at major Thai hospitals. Investigators will monitor for known CAR-T toxicities and measure remission rates and short-term survival outcomes.

Who should consider this trial

Good fit: Children aged 1–18 with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia who have received at least one prior therapy and meet required performance and organ function criteria are the intended participants.

Not a fit: Patients with CD19-negative disease, severe organ dysfunction, uncontrolled active infections, or those outside the pediatric age range are unlikely to benefit or may be ineligible.

Why it matters

Potential benefit: If successful, this approach could help more children with relapsed or refractory B-cell ALL achieve remission when other treatments have failed.

How similar studies have performed: Prior CD19-targeted CAR T-cell programs have produced high remission rates (often 70–90%) in relapsed/refractory B-ALL, while the IL-7Rα modification is a novel change with limited clinical data so far.

Eligibility criteria

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.

Where this trial is running

Bangkok, Bangkoknoi and 2 other locations

• Siriraj Hospital — Bangkok, Bangkoknoi, Thailand (Not_yet_recruiting)
• Maharaj Nakorn Chiang Mai Hospital — Chiang Mai, Mueang Chiang Mai District, Thailand (Not_yet_recruiting)
• King Chulalongkorn Memorial Hospital — Bangkok, Pathumwan, Thailand (Recruiting)

Study contacts

• Principal investigator: Kanhatai Chiengthong, MD — King Chulalongkorn Memorial Hospital
• Study coordinator: Piti Techavichit, Associate Professor, MD

Conditions Relapse B Acute Lymphoblastic Leukemia; Refactory Childhood Acute Lymphoblastic Leukemia; CAR T cell; CD19; IL-7 receptor alpha; Chimeric antigen receptor T cell; Adoptive cellular therapy; B-cell acute lymphoblastic leukemia