Evaluation of Long-term Safety in Paediatric Patients With B-precursor Acute Lymphoblastic Leukemia (ALL) who Have Been Treated With Either Blinatumomab or Chemotherapy (20180130) (Paediatric long-term follow up study)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  BLINCYTO
• Study drug International non-proprietary name (INN) or common name:
  BLINATUMOMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01FX07) blinatumomab

  blinatumomab
• Medical condition to be studied:
  B-cell type acute leukaemia

Population studied

• Short description of the study population:
  Paediatric (< 18 years old) patients who initiated treatment with either blinatumomab or SOC chemotherapy will be invited to participate in the study.
• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Estimated number of subjects:
  297

Study design details

• Study design:
  This study is an ambidirectional (retrospective and prospective) observational study.
• Main study objective:
  The overarching aim of this study is to describe the long-term safety profile of B-precursor ALL paediatric patients who have been treated with blinatumomab or chemotherapy
• Setting:
  Patients will be recruited from clinical study sites from countries
• Comparators:
  chemotherapy
• Outcomes:
  • To describe longitudinal trajectories of questionnaire-based neuropsychomotor developmental functioining, to enable the identification of long-term neuropsychomotor developmental impairment.; • To estimate incidence of endocrine impairment, neurological impairment, and immune system impairment (including autoimmune disorders and vaccine failure), ; • To estimate the incidence of allogenic Haemopoietic Stem Cell Transplant (alloHSCT) related adverse events (AEs); • To estimate the incidence of subsequent relapse of leukemia including in the central nervous system (CNS); • To estimate the cumulative incidence of long term AEs; • To estimate the incidence of secondary malignant formation; • To descriptively summarize mortality events
• Data analysis plan:
  Outcomes will be summarized using standard descriptive methods, including summary statistics for continuous variables, proportions for categorical variables, and 95% confidence intervals where appropriate. Time-to-event endpoints will be described using Kaplan-Meier methods.; ; Longitudinal neuropsychomotor developmental functioning will be assessed using annual Vineland and BRIEF questionnaire domain scores collected during follow-up. Changes in scores over time will be evaluated using mixed-effects models that account for repeated measurements within patients and differences in visit timing. Additional analyses will identify patients with persistent or clinically meaningful impairment using pre-specified score thresholds and changes from baseline. Models will adjust for relevant baseline and clinical factors, including age, sex, study site, and other pre-specified covariates.; ; The feasibility of comparative analyses between blinatumomab and standard-of-care chemotherapy will be assessed. Comparative analyses will only be performed if the treatment groups are considered sufficiently comparable. If feasible, propensity score methods will be used to improve comparability between treatment groups, followed by weighted analyses to estimate comparative effects for binary endpoints, reported as odds ratios with 95% confidence intervals.