Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma
A Phase 1/2 Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma
Roberto Chiarle
42 participants
Jan 31, 2025
INTERVENTIONAL
Conditions
Summary
This Phase 1/2 trial aims to determine the safety and feasibility of administration of autologous chimeric antigen receptor (CAR) T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor in pediatric subjects with relapsed or refractory neuroblastoma (NB). The trial will be conducted in two phases: Phase 1 will determine the maximum tolerated dose (MTD) of autologous hALK.CAR T cells using a 3+3 dose escalation design. Phase 2 will be an expansion phase to determine rates of response to hALK.CAR T cells.
Eligibility
Inclusion Criteria11
- 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
- Disease Status:
- Patients must have histologic verification of neuroblastoma at diagnosis or at relapse
- Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment
- Patients must have persistent/refractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol
- Patients must have evaluable or measurable disease per the revised International Neuroblastoma Response Criteria (INRC)
- Adequate washout from prior treatment regimens
- Adequate organ function
- Adequate performance status defined as Lansky or Karnofsky performance score ≥50%
- Subjects of reproductive potential must agree to use acceptable birth control methods
- Signed informed consent
Exclusion Criteria13
- Pregnant or nursing (lactating) women
- Patients with uncontrolled active infection
- Patients who are concurrently receiving other investigational agents
- 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
- 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
- Uncontrolled CNS metastasis
- CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement which may impair the ability to evaluate neurotoxicity
- History of severe hypersensitivity reaction to compounds used in the study
- HIV/HBV/HCV infection
- Patients receiving systemic steroid therapy (physiologic replacement, inhaled steroids and premedication for blood products are allowed)
- Primary immunodeficiency or history of systemic autoimmune disease requiring systemic immunosuppression/disease modifying agents within the last 2 years
- Uncontrolled intercurrent illness
- Inability to comply with the study requirements
Interventions
Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06803875