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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Autologous hALK.CAR T cells
  Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor

Первичные конечные точки

• Phase 1: Determine the Maximum Tolerated Dose (MTD) of hALK.CAR T cells [Срок оценки: 5 years]
• Phase 1: Evaluate Manufacturing Feasibility of hALK.CAR T cells [Срок оценки: 5 years]
• Phase 2: Estimate Response Rates [Срок оценки: Up to 5 years]

Вторичные конечные точки (5)

• Phase 1: Estimate Response Rates [Срок оценки: 5 years]
• Estimate Progression Free Survival and Overall Survival [Срок оценки: 5 years]
• Evaluate Patient-Reported Symptoms [Срок оценки: Up to 5 years]
• Persistence of hALK.CAR T cells [Срок оценки: Up to 5 years]
• Cytokine levels in the peripheral blood [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Boston Children's Hospital — Boston
• Dana-Farber Cancer Institute — Boston

Публикации

• Bergaggio E, Tai WT, Aroldi A, Mecca C, Landoni E, Nuesch M, Mota I, Metovic J, Molinaro L, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco RB, Li T, Klein D, Irvine DJ, Papotti M, Savoldo B, Dotti G, Chiarle R. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell. 2023 Dec 11;41(12):2100-2116.e10. doi: 10.1016/j.ccell.2023.11.004. Epub 2023 Nov 30 PMID 38039964

Идентификаторы

NCT: NCT06803875 · 24-392

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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