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

This study consists of two phases. The primary objectives of Phase 1 and Phase 2 are:

Phase 1:

• To identify the maximum tolerated dose (MTD) of autologous hALK.CAR T cells, and the recommended phase 2 dose (RP2D) in participants with relapsed/refractory high-risk neuroblastoma.
• To evaluate the feasibility of manufacturing autologous hALK.CAR T cells.

Phase 2:

To estimate the complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of participants with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells.

Inclusion criteria

• 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 criteria

• 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