Prospective, international, non-interventional study to assess the short- and long-term safety and effectiveness of adult patients with relapsed or refractory B cell acute lymphoblastic leukemia receiving Aucatzyl® treatment (AUTO1-LT2)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  This study will use secondary data from the EBMT and CIBMTR cellular therapies registry and will include data from patients who have been treated with Aucatzyl in the post-approval setting.

Study drug and medical condition

• Medicinal product name, other:
  aucatzyl; obecabtagene autoleucel
• Anatomical Therapeutic Chemical (ATC) code:
  (L01XL12) obecabtagene autoleucel

  obecabtagene autoleucel
• Medical condition to be studied:
  Precursor B-lymphoblastic lymphoma refractory

  Precursor B-lymphoblastic lymphoma recurrent

Population studied

• Short description of the study population:
  Patients aged 18 and over, diagnosed with r/r B ALL who have been treated with Aucatzyl at participating centers who have consented to share their pseudonymized data with Autolus.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  500

Study design details

• Study design:
  This study will use secondary data from the EBMT and CIBMTR cellular therapies registry and will include data from patients who have been treated with Aucatzyl in the post approval setting.
• Main study objective:
  To characterize the short- and long-term safety of Aucatzyl (in the treatment of r/r B ALL). Specifically, the rates and severity (where applicable) of the following AEs:; • CRS, including HLH/MAS.; • ICANS.; • Prolonged cytopenia.; • Hypogammaglobulinemia.; • Clinically significant infections.; • Secondary malignancies.; • Other neurologic toxicities.; • TLS.; • Immunogenicity, defined as hypersensitivity reactions.; • Aggravation of GvHD.; • New occurrence of an autoimmune disorder.; • Overdose. ; • Other safety concerns not yet identified in the clinical program.; • To evaluate pregnancy outcomes.
• Setting:
  This study will use secondary data from the EBMT and CIBMTR cellular therapies registry and will include data from patients who have been treated with Aucatzyl in the post approval setting and who consented to share the data with Autolus. This study will follow patients for up to 15 years following Aucatzyl infusion.; Participating centers will enter data directly into the CIBMTR and EBMT databases using electronic case report forms and will follow registry-specific procedures and requirements. The treatment centers will complete the data collection forms per the defined registry schedules. Patients must consent to have their data reported in the registry and to submit pseudonymized data (patient-level data) to Autolus. As this is a non-interventional study, no specific visit schedule is mandated.
• Outcomes:
  For the primary endpoints, the number and percentage of patients who experience at least 1 occurrence of the given event will be summarized for each risk defined in the primary endpoints. The severity will be summarized where applicable, including CRS, ICANS, TLS, and GvHD. Furthermore, annual incidence rates adjusted for follow-up duration will be calculated with the appropriate time periods and methods for relevant risks requiring long-term follow-up (e.g., secondary malignancies).; Time to onset of an AE will be summarized using appropriate methods. Time to onset of long term risks (e.g., any secondary malignancy) will be analyzed using competing risk method with death before experiencing an AE treated as competing event. Competing risk analysis will be performed for secondary malignancies, aggravation of GvHD, and autoimmune disorders. ; The analyses of the primary endpoints will be pooled between CIBMTR and EBMT where feasible. ; Subgroup analyses may be considered to explore the potential risk factors, including: ; • Age categories: ≤ 25 versus 26-54 versus ≥ 55.; • Age category: ≥ 26.; • Patients who receive OOS product.
• Data analysis plan:
  This study seeks to emulate the rigor of a prospective trial while leveraging the extensive RWD collected by the EBMT and CIBMTR registries. By recruiting patients across diverse geographic and clinical settings, the study aims to capture a broad and representative sample of treatment practices and patient outcomes. Endpoint definitions and response harmonization ensure alignment with prospective trial standards, enhancing the study’s generalizability and relevance to clinical practice.; The analysis will be performed for all patients who received at least 1 Aucatzyl infusion in this study. The data from EBMT and from CIBMTR will be analyzed separately and combined as appropriate. Categorical data will be summarized by the number and percentage of patients. Continuous data will be summarized using sample size, mean, standard deviation, median, Q1, Q3, minimum, and maximum. Time to event data will be summarized using KM estimators.