ALL SCT

Acute lymphblastic leukeamia

Open, randomised, multicentre, controlled, prospective phase III study

Background

Children an adolescents with lymphoblastic leukeamia can be cured with modern therapies in more than 80%. Nevertheless patients with high risk or relapsed acute lymphoblastic leukaemia (ALL) have a poor prognosis. For these patients intensive therapy is required after they have achieved remission with multimodal chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) can effectively induce immunological antileukaemic control in patients with ALL by means of the graft-versus-leukaemia effect (GvL), but treatment related mortality (TRM), morbidity and late effects remain serious problems of this treatment modality. In the last decade the short term outcome of 900 children with ALL from more than 60 different study centres who received allogeneic HSCT has improved, due to the use of donors more closely matched by Human leukocyte antigen (HLA) typing, resulting in less severe graft vs host disease (GvHD) and better supportive care. However, the risk of life long complications persists in all children. The observation and documentation of late complications are especially important for children and adolescents.

Rationale

The biggest burdens for children given TBI are the risks of long term complications as secondary malignancies, growth retardation (especially if irradiated below 10 years) and infertility (most common after irradiation during or after puberty). This is why "ALL-SCTped Forum" explores the question, if TBI can be replaced by a less toxic combination of different chemotherapies.

Ende der Patientenaufnahme um 01.04.2022: alle Patienten sollten nach den Standarts entsprechend des Spendertyps behandelt werden. In Planung ist die Eröffnung eines Registers bis zum Start der Nachfolgestudie.

Stratum 1

All patients > 4 years with a Matched Donor (MD) or Matched Sibling Donor (MSD) will be randomized between the conditioning with VP16/TBI or a Chemo-Conditioning (Busulfan/Thiatepa/Fludarabin or Treosulfan/Fludarabin/R´Thiotepa).

Stratum 2

Patients with a missmatched donor (MMD) will be stratified depending of the treatment centre. As Stem cell source has to be used an classical mismatched donor, a haploidentical donor or, cord blood. MMD transplanted patients receive stratified to the country a non-TBI chemo-conditioning with Fludarabine/Thiotepa/Treosulfan or Fludarabin/Thiotepa/Busulfan.

Patients ≤ 4 years are not randomized and receive a non-TBI chemo-conditioning ( Fludarabin/Thiotepa/Treosulfan or Fludarabin/Thiotepa/Busulfan).

• Age at time of screening less than 18 years
• Indication for allogeneic HSCT
• Complete remission (CR) before SCT
• Written consent of the parents (legal guardian) and, if necessary, the minor patient via “Informed Consent Form”
• No pregnancy
• ALL is no secondary malignancy
• No previous HSCT
• HSCT is performed in a study participating centre

• Patients who do not fulfil the inclusion criteria
• Non Hodgkin-Lymphoma
• ALL with extramedullary involvement with indication for TBI
• CNS involvement at screening timepoint
• Trisomie 21
• The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
• No consent is given for saving and propagation of anonymous medical data for study reasons
• Severe concomitant disease that does not allow treatment according to the protocol at the investigator’s discretion (e.g. malformation
• syndromes, cardiac malformations, metabolic disorders)
• Karnofsky / Lansky score < 50%
• Subjects unwilling or unable to comply with the study procedures