Co-administration of CART22-65s and huCART19 for B-ALL

NCT ID: NCT05674175

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-25
• Study Completion Date: 2029-01-15

Brief 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.

Conditions

B-cell Acute Lymphoblastic Leukemia; B Lineage Lymphoblastic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Finding Arm

Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities

Group Type: EXPERIMENTAL

Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)

Intervention Type: BIOLOGICAL

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

Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

Intervention Type: BIOLOGICAL

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

Expansion Arm

If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) \& Cohort B (prior treatment with a prior CAR T cell product).

Group Type: EXPERIMENTAL

Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)

Intervention Type: BIOLOGICAL

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

Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

Intervention Type: BIOLOGICAL

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

Interventions

Autologous, 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

Intervention Type: BIOLOGICAL

Autologous, 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

Intervention Type: BIOLOGICAL

Other Intervention Names

CART22-65s; huCART19

Eligibility Criteria

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

• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Stephan Grupp MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Stephan Grupp MD PhD

Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Regina Myers, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

CART Nurse Navigator

Role: CONTACT

CARTNurseNavigator@chop.edu

445-942-5891

Melissa S. Varghese, M.S.

Role: CONTACT

varghesem@chop.edu

8455535358

Facility Contacts

CART Nurse Navigator

Role: primary

cartnursenavigator@chop.edu

445-942-5891

Melissa Varghese, M.S.

Role: backup

varghesem@chop.edu

8455535358

Other Identifiers

22CT015

Identifier Type: OTHER

Identifier Source: secondary_id

22-020640

Identifier Type: -

Identifier Source: org_study_id