New CAR T-cell therapy for pediatric B-ALL

Phase I Dose Escalation and Preliminary Efficacy Study of Bispecific CD19 and CD22 Chimeric Antigen Receptor Co-Expressing T Cells (CD19x22 CAR T) in Pediatric Patients With Relapsed and/or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL)

This study is testing a new type of CAR T-cell therapy for children with tough-to-treat B-cell leukemia to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 3 Months to 30 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT06559189 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of a novel bispecific CAR T-cell therapy targeting both CD19 and CD22 in children with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). The therapy aims to address the limitations of current CD19-targeted treatments, particularly in patients who have experienced CD19-negative relapses. By utilizing a bispecific approach, the study seeks to improve treatment outcomes for pediatric patients who have not responded to standard therapies. Participants will undergo leukapheresis to collect T-cells, which will then be modified to express the bispecific CAR before being reinfused into the patient.

Who should consider this trial

Good fit: Ideal candidates include pediatric patients aged 3 months to 30 years with relapsed or refractory B-ALL who have CD19 and/or CD22 present on their last disease evaluation.

Not a fit: Patients who have not relapsed or are not refractory to standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for pediatric patients with difficult-to-treat B-ALL, potentially improving remission rates and reducing the risk of relapse.

How similar studies have performed: Other studies have shown promising results with CAR T-cell therapies, but this bispecific approach is relatively novel and untested in this specific patient population.

Eligibility 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 that is progressive despite other therapies or leading to CNS symptoms (including but not limited to: seizures, paresis, aphasia, hemorrhage, dementia, psychosis, or movement disorders) 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 or EKG) 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. Subjects of childbearing or child-fathering potential that are not willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the investigational product
6. Known HIV infection or active Hepatitis B or Hepatitis C infection.

Where this trial is running

Aurora, Colorado

• Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Vanessa Fabrizio, MD — University of Colorado, Denver
• Study coordinator: Vanessa Fabrizio, MD

Conditions B-cell Acute Lymphoblastic Leukemia; Pediatric; Relapsed; Refractory; Hematologic diseases