Treatment for specific types of pediatric and young adult leukemia using engineered T cells

CD19-Directed Chimeric Antigen Receptor CD19 Redirected Autologous T Cells (CART19) for Orphan Indications of Pediatric B Cell Acute Lymphoblastic Leukemia (B ALL)

This study is testing a special type of T cell therapy to see if it can help young patients with certain high-risk forms of leukemia feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 133 (estimated)
• Ages: 0 Years to 29 Years
• Sex: All
• Sponsor: Children's Hospital of Philadelphia (other)
• Drugs / interventions: prednisone, radiation
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT04276870 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial evaluates the efficacy of CART19, a type of engineered T cell therapy, in pediatric and young adult patients with specific high-risk forms of B-cell acute lymphoblastic leukemia (B-ALL). The study consists of four cohorts targeting patients with hypodiploid B-ALL, those with the t(17;19) chromosomal translocation, infants with very high-risk KMT2A B-ALL, and patients experiencing central nervous system relapse without prior cranial radiation or bone marrow transplantation. Participants will receive murine CART19 therapy, and the study aims to assess treatment outcomes in these vulnerable populations.

Who should consider this trial

Good fit: Ideal candidates include pediatric and young adult patients with specific genetic markers associated with high-risk B-ALL.

Not a fit: Patients with other forms of leukemia or those who have already undergone cranial radiation or bone marrow transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with high-risk leukemia who currently have limited treatment alternatives.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results in treating various forms of leukemia, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any study procedure.
2. Male and female patients with documented CD19+ B-ALL

   a.Cohort A \& B: Patients, regardless their response to initial or relapsed B ALL therapy, with the following characteristics: i.Cohort A: Subjects with confirmation of a hypodiploid karyotype (chromosome number fewer than 45) ii.Cohort B: Subjects with cytogenetic confirmation of the chromosomal translocation t(17;19) (Cohort B) b.Cohort C: Infants w/ newly diagnosed KMT2A rearranged B-ALL classified as very high risk by the following criteria: i.Age \< 3 months at diagnosis ii.Age \< 6 months and WBC \> 300,000x109/L at diagnosis or a poor prednisone response in induction iii.MRD positive \> 0.01 (or PCR \> 104) after 2 courses of standard infant ALL therapy.

   c.Cohort D: Subjects in a first or greater CNS relapse, prior to therapy with cranial XRT or HSCT for the current relapse
3. Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue.
4. Age 0 to 29 years
5. Adequate organ function defined as:

   1. A serum creatinine based on age/gender as follows:

      Maximum Serum Creatinine (mg/dL) Age Male Female 0 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1.0 1.0 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4

      ≥ 16 years 1.7 1.4
   2. Adequate liver function:

   i.ALT≤ 5 x ULN; ALT ii.Total bilirubin ≤ 3 x ULN iii.ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.

   c.Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \< Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the physician-investigator.

   d.Left Ventricular Shortening Fraction (LVSF) ≥ 28%, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% by echocardiogram. In cases where quanitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualititatively normal ventricular function wll suffice.
6. Adequate performance status defined as Lansky or Karnofsky score ≥ 50
7. Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria:

1. For subjects with a CNS relapse, prior cranial XRT or BMT for the current relapse is an exclusion.
2. Active hepatitis B or active hepatitis C.
3. HIV Infection.
4. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
5. Concurrent use of systemic steroids 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 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.
6. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
7. Pregnant or nursing (lactating) women.
8. Uncontrolled active infection.

Where this trial is running

Philadelphia, Pennsylvania

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Amanda DiNofia, MD — Children's Hospital of Philadelphia
• Study coordinator: CART Nurse Navigator

Conditions: Pediatric and Young Adult Patientswith Hypodiploid or t(17, 19) B-ALL, Infants With Very High Risk KMT2A B-ALL, Patients With Central Nervous System Relapse Who Did Not Receive Cranial Radiation or Bone Marrow Transplantation