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NCT06559189 | RECRUITING | B-cell Acute Lymphoblastic Leukemia

CD19x22 Chimeric Antigen Receptor T-cell Therapy (CAR T) in Pediatric B-ALL
Sponsor:

University of Colorado, Denver

Brief Summary:

This study will evaluate the safety and tolerability of administering a novel bispecific CD19/CD22-directed CAR T cell product (CD19x22) for the treatment of relapsed or refractory pediatric B-ALL.

Condition or disease

B-cell Acute Lymphoblastic Leukemia

Intervention/treatment

CD19x22 CAR T

Phase

PHASE1

Detailed Description:

Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) is the most common type of hematologic malignancy in the pediatric population (ages 0-19). Despite favorable prognosis in pediatric B-ALL as a whole, outcomes remain poor for patients who have relapsed or are refractory (R/R) to standard therapies. The Federal and Drug Administration (FDA) approved CD19-directed chimeric antigen receptor T-cell therapy (CAR T cell) based on an 80+% remission induction rate thus expanding treatment options for this subtype of leukemia. However, despite the high remission rates induced by CD19-directed CAR T cell therapy, the current FDA-approved chimeric antigen receptor therapies (CARs) have limitations associated with the durability of response. Additionally, relapse due to loss of the targeted antigen (CD19 negative) is a frequent cause of resistance to CD19-targeted cell therapy. This study will investigate a novel bispecific CD19/CD22-directed CAR T cell product (CD19x22). This CAR T cell therapy can be used in patients with CD19-negative relapse after initial CD19-targeted cell therapy or in naive CAR T cell patients with the goal of reducing CD19-negative relapses.

Study Type : INTERVENTIONAL
Estimated Enrollment : 26 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : Phase I Dose Escalation and Preliminary Efficacy Study of Bispecific CD19 and CD22 Chimeric Antigen Receptor Co-Expressing T Cells [CD19x22 Chimeric Antigen Receptor T-cell Therapy (CAR T)] in Pediatric Patients with Relapsed And/or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Actual Study Start Date : 2024-09-27
Estimated Primary Completion Date : 2028-12
Estimated Study Completion Date : 2029-12

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 3 Months to 30 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • 1. Subjects must have a history of B precursor ALL with any of the following conditions
    • 1. Relapsed two or more times.
    • 2. Relapsed at any time after allogeneic bone marrow transplant (BMT).
    • 3. Relapse or refractory after single antigen targeting CAR T cell therapy.
    • i. 90 days must have elapsed post previous CAR infusion prior to apheresis. d. Refractory to standard therapy as determined by the treating physician. e. Patient and/or parents declining BMT options and would prefer CAR T Therapy.
    • 2. CD19 and/or CD22 present on last relapsed/refractory disease evaluation.
    • 3. Performance score (Lansky or Karnofsky ≥ 50%; or Eastern Cooperative Oncology Group (ECOG) must be ≤2).
    • 4. Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines.
    • 5. Males OR non-pregnant, non-lactating females.
    • 6. Aged 3 months to 30 years (inclusive) at time of consent and enrollment.
    • 7. Provision of a signed and dated consent form from parent or guardian (patients \< 18), the patient themselves (\> 18), or legally authorized representative (patient \> 18 who lack decision-making capacity) after standard of care (SOC) screening assessments are performed.
    • 8. Stated willingness to comply with all study procedures and be available for the duration of the study.
    • 9. Willingness to participate in long-term follow-up protocol.
    Exclusion Criteria
    • 1. Active, uncontrolled central nervous system (CNS) leukemia as determined by the treating physician at eligibility, prior to lymphodepleting chemotherapy (LD chemo), and pre- CD19x22 CAR T cell infusion.
    • 2. History of allogeneic stem cell transplantation prior to apheresis that meet the following criteria
      • 1. Less than 100 days post-transplant;
      • 2. Evidence of active Graft-versus-Host Disease (GvHD) requiring systemic therapy;
      • 3. Less than 6 weeks post donor lymphocyte infusion (DLI).
      • 3. Active, uncontrolled, life-threatening infection that at the determination of the treating physician would preclude safe apheresis or tolerance of lymphodepleting chemotherapy, cell infusion, or increased risk of cytokine release syndrome.
      • 4. Evidence of severe organ dysfunction defined by
        • 1. Baseline oxygen saturation of \< 90% on room air
        • 2. Myocardial dysfunction (based on age standards): Ejection fraction ≤\< 40% or shortening fraction ≤ 28%,, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings
        • 3. Transaminases \> 10x upper limit of normal (ULN) or bilirubin \> 5x the ULN, unless thought to be related to primary disease
        • 4. Estimated Creatinine (Cr) clearance \< 60 mL/min/1.73 m2 (if nuclear medicine GFR or other more specific testing exceeds this level than it can supersede the estimated clearance)
        • 5. Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.
        • 6. Known HIV infection or active Hepatitis B or Hepatitis C infection.
CD19x22 Chimeric Antigen Receptor T-cell Therapy (CAR T) in Pediatric B-ALL

Location Details

NCT06559189

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Locations

RECRUITING

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045