RECRUITING

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

Conditions

B-cell Acute Lymphoblastic Leukemia Pediatric Relapsed Refractory Hematologic diseases

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2024-09-27

Study Completion:2029-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06559189

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Months to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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. 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.	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.

Inclusion Criteria

Exclusion 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.
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.

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.

Contacts and Locations

Study Contact

Vanessa Fabrizio, MD

CONTACT

720-777-6860

BMT@childrenscolorado.org

Principal Investigator

Vanessa Fabrizio, MD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

Vanessa Fabrizio, MD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-27

Study Completion Date2029-12

Study Record Updates

Study Start Date2024-09-27

Study Completion Date2029-12

Terms related to this study

Keywords Provided by Researchers

Pediatric
Relapsed
Refractory
B-cell Acute Lymphoblastic Leukemia
Hematologic diseases

Additional Relevant MeSH Terms

B-cell Acute Lymphoblastic Leukemia