Clinical trial NCT05674175: Co-administration of CART22-65s and huCART19 for B-ALL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
B Lineage Lymphoblastic Lymphoma
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
First posted: 2023-01-06
Enrollment: 93
Sex: ALL
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of CART22-65s and huCART19 co-administration
timeFrame: 1 year
measure: Efficacy of CART22-65s and huCART19 co-administration
timeFrame: 1 year
Secondary outcomes:
measure: Manufacturing Feasibility
timeFrame: 5 years
measure: Anti-tumor response due to CART22-65s and huCART19 co-administration
timeFrame: Day 28
measure: Event Free Survival
timeFrame: 1 year
measure: Relapse Free Survival
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
measure: CAR T Cell Therapy Persistence
timeFrame: 1 year
measure: Bioreactivity of CART22-65s and huCART19 when co-administered
timeFrame: 1 year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Regina Myers, MD
role: PRINCIPAL_INVESTIGATOR
References: