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)

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).

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).

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia; Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: AUTO1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Autolus Ltd; Phone Number: +44 (0) 203 911 4385; Email: clinicaltrials@autolus.com

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Vall d'Hebron
    • Principal Investigator: Cristina Diaz de Heredia, MD
  • Madrid, Spain
    • Recruiting
    • Hospital Niño Jesús
    • Principal Investigator: Alba Rubio, MD
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital For Children NHS Foundation Trust
    • Principal Investigator: Dr Juliana Silva, MD
  • Manchester, United Kingdom
    • Recruiting
    • Royal Manchester Children's Hospital
    • Principal Investigator: Denise Bonney, MD
  • Newcastle upon Tyne, United Kingdom
    • Recruiting
    • Great North Children's Hospital
    • Principal Investigator: Geoff Shenton, MD
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Shannon Maude, MD
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Methodist Children's Hospital
      • Principal Investigator: Amanda Lipsitt, MD
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • Primary Children's Hospital
      • Principal Investigator: Michael Pulsipher, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

• < 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.

EXCLUSION CRITERIA:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AUTO1	Biological: AUTO1; Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with anti-CD19 chimeric antigen receptor (CAR) T cells; Other Names: Obecabtagene autoleucel (obe-cel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)	Up to 24 months
Incidence and duration of severe hypogammaglobulinemia	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	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response in B NHL	Up to 24 months
Incidence of CD19-negative relapse at any time in B NHL	Up to 24 months
Event-free survival in B ALL	Up to 24 months
Progression-free survival in B NHL	Up to 24 months
Overall survival (OS) in B ALL	Up to 24 months
CR per IRRC assessment at any time in B ALL	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	Up to 24 months
Minimal residual disease (MRD)-negative ORR per IRRC assessment at any time in B ALL	Up to 24 months
ORR (CR or partial response [PR]) per Investigator assessment occurring at any time in B NHL	Up to 24 months
OS in B NHL	Up to 24 months

Collaborators and Investigators

• Sponsor: Autolus Limited

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: B cell acute lymphoblastic leukemia; Relapsed B cell acute lymphoblastic leukemia; Refractory B cell acute lymphoblastic leukemia; CD19-positive CAR T cell; Pediatric ALL; B cell Non-Hodgkin lymphoma; Relapsed B cell Non-Hodgkin lymphoma; Refractory B cell Non-Hodgkin lymphoma; Aggressive mature B cell Non-Hodgkin lymphoma; Pediatric NHL; Obecabtagene autoleucel; Obe-cel
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, Lymphoid; Leukemia; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma
• Other Study ID Numbers: AUTO1-PY1; 2023-506307-26-00 (Other Identifier: EU CT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No