A Study of CD19 Targeted CAR T Cell Therapy in Pediatric Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL)

Официальное название

A Single-Arm, Open-Label, Multicenter, Phase 1b/2 Study Evaluating the Safety and Efficacy of AUTO1 (Obecabtagene Autoleucel [Obe-cel]) in Pediatric Patients With CD19-positive Relapsed/Refractory (R/R) B Cell Acute Lymphoblastic Leukemia (B ALL) or R/R Aggressive Mature B Cell Non-Hodgkin Lymphoma (B NHL).

Обзор

This is a Phase 1b/2 study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 in pediatric patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B ALL) and r/r B cell Non-Hodgkin lymphoma (B NHL).

Подробное описание

This is a single-arm, open-label, multi-center, Phase 1b/2 study to determine the safety and efficacy of obe-cel administered intravenously in pediatric patients \< 18 years old with r/r B ALL and with r/r aggressive mature B NHL.

The safety and tolerability of obe cel in pediatric patients will be continually monitored by the Sponsor. Efficacy endpoints will be determined by an Independent Response Review Committee (IRRC).

The study will involve consented patients going through the following sequential study periods: screening, leukapheresis, bridging as necessary, lymphodepletion, treatment evaluation, and follow-up.

Вмешательства

• Биопрепарат AUTO1
  Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with anti-CD19 chimeric antigen receptor (CAR) T cells

Первичные конечные точки

• Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Up to 24 months]
• Incidence and duration of severe hypogammaglobulinemia [Срок оценки: Up to 24 months]
• Proportion of pediatric participants with r/r B ALL at screening who achieve complete remission (CR) within 3 months of obe-cel infusion per Independent Response Review Committee (IRRC) assessment [Срок оценки: 3 months]

Вторичные конечные точки (10)

• CR per IRRC assessment at any time in B ALL [Срок оценки: Up to 24 months]
• Overall remission rate (ORR) (CR + complete remission with incomplete recovery of counts [CRi]) per IRRC assessment at any time in B ALL [Срок оценки: Up to 24 months]
• Minimal residual disease (MRD)-negative ORR per IRRC assessment at any time in B ALL [Срок оценки: Up to 24 months]
• Event-free survival in B ALL [Срок оценки: Up to 24 months]
• Overall survival (OS) in B ALL [Срок оценки: Up to 24 months]
• ORR (CR or partial response [PR]) per Investigator assessment occurring at any time in B NHL [Срок оценки: Up to 24 months]
• Duration of response in B NHL [Срок оценки: Up to 24 months]
• Progression-free survival in B NHL [Срок оценки: Up to 24 months]
• OS in B NHL [Срок оценки: Up to 24 months]
• Incidence of CD19-negative relapse at any time in B NHL [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• < 18 years old at screening
• ≥ 6 kg body weight at screening

Pediatric patients with r/r B ALL

r/r CD19-positive aggressive mature B including the B NHL subtypes: i) diffuse large B cell lymphoma, ii) Burkitt's lymphoma, iii) primary mediastinal large B cell lymphoma, iv) high-grade B cell lymphoma (not otherwise specified).

• Karnofsky (age ≥ 10 years) or Lansky (age < 10 year) performance status score ≥ 50%.
• In participants with B ALL, local documentation of CD19 expression on leukemic blasts in the BM, peripheral blood, or cerebrospinal fluid or biopsy done no more than 30 days prior to consent.
• Adequate renal, hepatic, pulmonary, and cardiac function.

Критерии исключения

• Diagnosis of chronic myelogenous leukemia in lymphoid blast crisis.
• History or presence of clinically relevant central nervous system (CNS) pathology unrelated to CNS leukemia.
• Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management.
• Received prior (< 3 months before obe cel infusion) stem cell transplantation.
• Prior CD19 targeted therapy other than blinatumomab.
• Experienced Grade ≥ 3 neurotoxicity following blinatumomab.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Children's Hospital of Philadelphia — Philadelphia
• Methodist Children's Hospital — San Antonio
• Primary Children's Hospital — Salt Lake City

Великобритания · 3 центра

• Great Ormond Street Hospital for Children NHS Foundation Trust — London
• Royal Manchester Children's Hospital — Manchester
• Great North Children's Hospital — Newcastle upon Tyne

Испания · 2 центра

• Hospital Vall d'Hebron — Barcelona
• Hospital Nino Jesus — Madrid

Публикации

• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. PMID 41671463

Идентификаторы

NCT: NCT06173518 · AUTO1-PY1 · 2023-506307-26-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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