Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies
Condition: Acute Lymphoblastic Leukaemias (ALL); Acute Myeloid Leukaemias (AML); Myelodysplastic Syndromes (MDS); Juvenile Myelomonocytic Leukaemias (JMML)
MeSH terms: Leukemia; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary goal of this study is to evaluate an alternative myeloablative, but reduced
      toxicity conditioning regimen in children, to describe the safety and efficacy of intravenous
      (i.v.) Treosulfan administered as part of a standardised Fludarabine-containing conditioning
      and to contribute to the current pharmacokinetic model to be able to finally give age (or
      body surface area) dependent dose recommendations. The treatment regimens given in the
      protocol MC-FludT.17/M are based on sufficient clinical safety and efficacy data. Considering
      the vital indication for allogeneic haematopoietic stem cell transplantation of the selected
      patient population, the risk-benefit assessment is therefore reasonably in favour of the
      study conduct.
    

Detailed description: 
      The protocol MC-FludT.17/M is a clinical phase II trial to describe the safety and efficacy
      of Treosulfan-based conditioning therapy prior to allogeneic haematopoietic stem cell
      transplantation (allo-HSCT) in at least 70 paediatric patients with haematological
      malignancies (male and female children with haematological malignant diseases as acute
      lymphoblastic leukaemias (ALL), acute myeloid leukaemias (AML), myelodysplastic syndromes
      (MDS) and juvenile myelomonocytic leukaemias (JMML), requiring myeloablative conditioning
      treatment with following allo-HSCT).

      Treosulfan dose per day is to be calculated by using body surface area (BSA). Two background
      conditioning regimens with Treosulfan are allowed: One regimen consists of a standardised
      Fludarabine-containing regimen and the other consists of an intensified regimen with
      Fludarabine and ThioTEPA.

      Freedom from transplant (treatment)-related mortality (TRM), defined as death from any
      transplant-related cause from the day of first administration of study medication until day
      +100 after HSCT is the primary objective of the trial.

      Moreover, the current pharmacokinetic (PK) model should be contributed to be able to finally
      give age (or BSA) dependent dose recommendations.
    

Intervention name(s): Treosulfan
Intervention type(s): Drug
Intervention description(s): Treosulfan dose per day is to be calculated by using BSA:
One dose of Treosulfan per day on three consecutive days (day -6, day -5 and day -4) as intravenous (i.v.) infusion, given over 2 hours.
Two background conditioning regimens with Treosulfan are allowed: One regimen consists of a standardised Fludarabine-containing regimen (regimen A) and the other consists of an intensified regimen with Fludarabine and ThioTEPA (regimen B). The investigator decides for each individual patient whether to treat the patient with regimen A or with regimen B.
Treosulfan: i.v., BSA adapted: 10, 12 or 14 g/m²/day within 120 min to be administered prior to Fludarabine; Fludarabine: i.v., 30 mg/m2/day on days from -7 to -3 prior to HSCT; ThioTEPA (Regimen B): i.v., 2 x 5mg/kg/day on day -2.
Other intervention name(s): Treograft®; Ovastat®
Intervention MeSH terms: Treosulfan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALL; AML; MDS; JMML