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

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  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

• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)
• Estimated number of subjects:
  298

Study design details

• 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 prior to undergoing haemopoietic stem cell transplant.
• Outcomes:
  • To estimate incidence of neuropsychomotor developmental impairment, endocrine impairment, neurological impairment, and immune system impairment (including autoimmune disorders and vaccine failure), ; • To estimate the incidence of Haemopoietic Stem Cell Transplant (HSCT) 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 estimate overall survival
• Data analysis plan:
  For categorical outcomes, 95% confidence intervals (CIs) will also be presented where appropriate. For time-to-event endpoints, Kaplan-Meier (KM) curves and KM proportions at select time points, the numbers of patients with events and then number of patients censored will be used to summarize the data. A comparison between the blinatumomab versus chemotherapy group will be conducted at the final follow-up in the study pending adequate sample size is enrolled (≥ 50 patients per arm) and the blinatumomab and SOC groups are comparable. Any covariates that are not comparable between the two will be evaluated as a covariate for adjustment in the models. A multivariate logistic regression will be used to compare incidence event objectives and Cox regression will be used to compare time-to-event objectives. Also, we will conduct a propensity score weighting analysis based on the covariates collected for this study.