Treatment with CAR T cells for high-risk neuroblastoma in children

A Phase 1/2 Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma

This study is testing a new CAR T cell treatment for children with hard-to-treat neuroblastoma to see if it is safe and how well it works.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 12 Months to 29 Years
• Sex: All
• Sponsor: Boston Children's Hospital (Academic / other)
• Drugs / interventions: CART, CAR T, chimeric antigen receptor
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT06803875 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial evaluates the safety and feasibility of using autologous chimeric antigen receptor (CAR) T cells that target the human Anaplastic Lymphoma Kinase (ALK) receptor in pediatric patients with relapsed or refractory high-risk neuroblastoma. The study is divided into two phases: Phase 1 focuses on determining the maximum tolerated dose (MTD) of the CAR T cells, while Phase 2 aims to assess the response rates to this treatment. Participants must have histologically verified neuroblastoma and meet specific eligibility criteria related to age, disease status, and organ function.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 12 months to 30 years with relapsed or refractory high-risk neuroblastoma.

Not a fit: Patients who are pregnant or have not achieved adequate organ function may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children with high-risk neuroblastoma who have exhausted standard treatment options.

How similar studies have performed: Other studies utilizing CAR T cell therapy have shown promising results in various cancers, suggesting potential success for this novel approach in neuroblastoma.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 12 months and \< 30 years at the time of consent. The first patient on each dose level will need to be age ≥ 6 years old
2. Disease Status:

   1. Patients must have histologic verification of neuroblastoma at diagnosis or at relapse
   2. Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment
   3. Patients must have persistent/refractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol
   4. Patients must have evaluable or measurable disease per the revised International Neuroblastoma Response Criteria (INRC)
3. Adequate washout from prior treatment regimens
4. Adequate organ function
5. Adequate performance status defined as Lansky or Karnofsky performance score ≥50%
6. Subjects of reproductive potential must agree to use acceptable birth control methods
7. Signed informed consent

Exclusion Criteria:

1. Pregnant or nursing (lactating) women
2. Patients with uncontrolled active infection
3. Patients who are concurrently receiving other investigational agents
4. Patients who have received prior CART-cell or other gene-modified immune-effector cell therapy, are not eligible unless they are \>8 weeks from time of infusion, have fully recovered from any associated toxicities and have documented lack of persistence of the product
5. Patients with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years
6. Uncontrolled CNS metastasis
7. CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement which may impair the ability to evaluate neurotoxicity
8. History of severe hypersensitivity reaction to compounds used in the study
9. HIV/HBV/HCV infection
10. Patients receiving systemic steroid therapy (physiologic replacement, inhaled steroids and premedication for blood products are allowed)
11. Primary immunodeficiency or history of systemic autoimmune disease requiring systemic immunosuppression/disease modifying agents within the last 2 years
12. Uncontrolled intercurrent illness
13. Inability to comply with the study requirements

Where this trial is running

Boston, Massachusetts and 1 other locations

• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Susanne Baumeister, MD — Dana-Farber Cancer Institute
• Study coordinator: Susanne Baumeister, MD

Conditions Relapsed Neuroblastoma; Refractory Neuroblastoma; High-risk Neuroblastoma; High-Risk Neuroblastoma