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Recruiting NCT05674175

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

Phase I / Phase II Interventional B-cell Acute Lymphoblastic Leukemia B Lineage Lymphoblastic Lymphoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s), Autologous, humanized anti-CD19 CAR T cell therapy (huCART19).
Who it may be relevant to
Registry conditions: B-cell Acute Lymphoblastic Leukemia, B Lineage Lymphoblastic Lymphoma. Basic parameters: up to 29 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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

Overview

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.

Interventions

  • Biological 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
  • 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

Primary outcome measures

  • Safety of CART22-65s and huCART19 co-administration [Time frame: 1 year]
  • Efficacy of CART22-65s and huCART19 co-administration [Time frame: 1 year]
Secondary outcome measures (7)
  • 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

Inclusion criteria

  • Signed informed consent form
  • Patients with documented CD19+ and/or CD22+ ALL/LLy:
  • Cohort A: Patients with relapsed or refractory ALL/LLy:
  • Cohort B: Patients with poor response to prior B cell directed engineered cell therapy
  • Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy
  • 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.
  • Age 0-29 years
  • Adequate organ function
  • Adequate performance status defined as Lanksy or Karnofsky performance score ≥50.
  • Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion criteria

  • Active hepatitis B or active hepatitis C
  • HIV infection
  • Active acute or chronic Graft Vs. Host Disease requiring systemic therapy
  • 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.
  • 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.
  • Pregnant or nursing (lactating) women
  • Uncontrolled active infection

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 1 center
  • Children's Hospital of Philadelphia — Philadelphia

Identifiers

NCT: NCT05674175 · 22-020640 · 22CT015

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗