RecruitingInterventionalPhase 1/Phase 2

Use of Autologous Anti-CD22 CAR T Cells (CART22-65s) Co-administered With Humanized Anti-CD19 CAR T Cells (huCART19) in Children and Young Adults With Relapsed or Refractory B-ALL

NCT ID: NCT05674175Sponsor: Stephan Grupp MD PhDLast updated: 2026-03-27

Summary

This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).

Detailed description

CD19-targeted CAR T cell therapy has transformed the treatment landscape for children and young adults with chemo-refractory or relapsed B cell Acute Lymphoblastic Leukemia (B-ALL). Despite remarkable initial response rates, approximately 50% of pediatric patients experience a subsequent disease relapse. The prognosis for these patients is dismal with a median survival of less than one year from the time of post-CART19 relapse. The primary mechanisms contributing to CART19 failure include CD19-antigen escape and loss of CAR T cell surveillance due to short CART persistence. This study aims to counter each driver of relapse by co-administering two next-generation CAR T cell products: an anti-CD22 CART (CART22-65s), designed to overcome CD19-antigen escape; and a humanized anti-CD19 CART (huCART19), designed to overcome immune-mediated rejection of murine CART19.

Arms & interventions

BiologicalAutologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)
CART22-65s are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD22 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain
BiologicalAutologous, humanized anti-CD19 CAR T cell therapy (huCART19)
HuCART19 cells are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD19 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain

Outcome measures

Primary

Safety of CART22-65s and huCART19 co-administration
The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory B-Cell Acute Lymphoblastic Leukemia or B Cell Lymphoblastic Lymphoma (B-LLy), including those previously treated with cell therapy.
Time frame: 1 year
Efficacy of CART22-65s and huCART19 co-administration
The efficacy of CART22-65s and huCART19 co-administration will be measured by the evaluating the overall response rate in patients with advanced or refractory B cell hematologic malignancies, including those previously treated with cell therapy.
Time frame: 1 year

Secondary

Manufacturing Feasibility
Time frame: 5 years
Anti-tumor response due to CART22-65s and huCART19 co-administration
Time frame: Day 28
Event Free Survival
Time frame: 1 year
Relapse Free Survival
Time frame: 1 year
Overall Survival
Time frame: 1 year
CAR T Cell Therapy Persistence
Time frame: 1 year
Bioreactivity of CART22-65s and huCART19 when co-administered
Time frame: 1 year

Eligibility criteria

Sex: AllAge: Up to 29 YearsHealthy volunteers: No

Inclusion Criteria: 1. Signed informed consent form 2. Patients with documented CD19+ and/or CD22+ ALL/LLy: 1. Cohort A: Patients with relapsed or refractory ALL/LLy: 2. Cohort B: Patients with poor response to prior B cell directed engineered cell therapy 3. Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy 4. Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression. 5. Age 0-29 years 6. Adequate organ function 7. Adequate performance status defined as Lanksy or Karnofsky performance score ≥50. 8. Subjects of reproductive potential must agree to use acceptable birth control methods. Exclusion Criteria: 1. Active hepatitis B or active hepatitis C 2. HIV infection 3. Active acute or chronic Graft Vs. Host Disease requiring systemic therapy 4. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well. 5. Central nervous system disease that is progressive on therapy, or with Central nervous system parenchymal lesions that might increase the risk of central nervous system toxicity. 6. Pregnant or nursing (lactating) women 7. Uncontrolled active infection

Study locations (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

Recruiting

CART Nurse Navigator · Contact

445-942-5891 cartnursenavigator@chop.edu

Melissa Varghese, M.S. · Contact

8455535358 varghesem@chop.edu