Clinical Trials /

Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia

NCT01949129

Description:

The ALL SCTped 2012 FORUM is a multinational, multi-centre, randomized, controlled, prospective seamless phase II/III study for the therapy and therapy optimisation for children and adolescents with ALL in CR, who have an indication for HSCT (hematopoetic stem cell transplantation) with a myeloablative conditioning regimen. The stratification and randomisation of patients in first and following remission according to the individual transplantation modalities rests upon an indication for allogeneic HSCT AND on the availability of a suitable donor within the individual transplantation groups. Main objectives - Objective 1: Randomisation of TBI vs non-TBI conditioning regimen for patients with a HLA matched-sibling donor or unrelated HLA matched donor. We aim at showing that a non-total body irradiation (TBI) containing conditioning (Flu/Thio/ivBu or Flu/Thio/Treo) results in a non-inferior survival as compared to conditioning with TBI/Etoposide in children older than 4 years after HSCT from a Human leucocyte antigen (HLA) identical sibling donor (MSD) or a HLA matched donor (MD). - Objective 2: Stratification of patients with a HLA mismatched donor according to stem cell source. We aim at exploring event free survival (EFS) after HSCT from HLA mismatched donors using mismatched unrelated donors (MMD), mismatched cord blood or HLA haplo-identical family members with non TBI-conditioning regimen.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia
  • Official Title: Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia

Clinical Trial IDs

  • ORG STUDY ID: ALL SCTped FORUM 2012
  • NCT ID: NCT01949129

Conditions

  • Acute Lymphoblastic Leukaemia

Interventions

DrugSynonymsArms
VP16Etoposideconditioning TBI/VP16
Thiotepaconditioning Flu/Thio/Treo or Flu/Thio/ivBu
Treosulfanconditioning Flu/Thio/Treo or Flu/Thio/ivBu
Fludarabineconditioning Flu/Thio/Treo or Flu/Thio/ivBu
Busulfanconditioning Flu/Thio/Treo or Flu/Thio/ivBu

Purpose

The ALL SCTped 2012 FORUM is a multinational, multi-centre, randomized, controlled, prospective seamless phase II/III study for the therapy and therapy optimisation for children and adolescents with ALL in CR, who have an indication for HSCT (hematopoetic stem cell transplantation) with a myeloablative conditioning regimen. The stratification and randomisation of patients in first and following remission according to the individual transplantation modalities rests upon an indication for allogeneic HSCT AND on the availability of a suitable donor within the individual transplantation groups. Main objectives - Objective 1: Randomisation of TBI vs non-TBI conditioning regimen for patients with a HLA matched-sibling donor or unrelated HLA matched donor. We aim at showing that a non-total body irradiation (TBI) containing conditioning (Flu/Thio/ivBu or Flu/Thio/Treo) results in a non-inferior survival as compared to conditioning with TBI/Etoposide in children older than 4 years after HSCT from a Human leucocyte antigen (HLA) identical sibling donor (MSD) or a HLA matched donor (MD). - Objective 2: Stratification of patients with a HLA mismatched donor according to stem cell source. We aim at exploring event free survival (EFS) after HSCT from HLA mismatched donors using mismatched unrelated donors (MMD), mismatched cord blood or HLA haplo-identical family members with non TBI-conditioning regimen.

Detailed Description

      Acute and late side effects of TBI in combination with other chemotherapeutic are manifold to
      the growing organism and include severe organ dysfunction/failure due to toxicity. Although
      transplant associated mortality was reduced after HSCT in the last decade due to better HLA
      matching, infection prevention and control, the burden of late complications is still a
      matter of concern.Growth retardation, hormonal dysfunction, sterility and the risk of
      secondary cancer are the late consequences of TBI in children.However, so far no prospective
      study has demonstrated similar outcomes in paediatric ALL using chemo-conditioning regimen
      before HSCT.The reason for that are manifold: only a minority of children with ALL qualify
      for allogeneic HSCT as most patients are cured with modern chemotherapy approaches alone.
      Those with dismal prognosis are treated in HSCT centres that care for patients with different
      diseases. Therefore it is nearly impossible to answer complex outcome questions in single
      centres or even in single countries. International cooperation are essential to allow
      prospective randomized investigation within comparable patient cohorts. This study aims to
      explore the efficacy and efficiency of two different chemo-conditioning regimens (Flu/Thio
      with Treo or ivBu) in comparison to the standard conditioning regimen (TBI/VP16). All
      patients with an indication for HSCT, age > 4 years and a matched donor (MD) or matched
      sibling donor (MSD) undergo randomisation between these two conditionings. The decision if
      the irradiation free conditioning is Flu/Thio/Treo or Flu/Thio/ivBu is stratified by country.
      Patients with age < 4 years receive automatically the irradiation free conditioning. Patients
      with a mismatched donor are stratified according to the donor's stem cell source (cordblood,
      haploidentical tx or bone marrow/peripheral blood stem cells).
    

Trial Arms

NameTypeDescriptionInterventions
conditioning Flu/Thio/Treo or Flu/Thio/ivBuExperimentalpatients > 4 years with a MSD or MD
  • Thiotepa
  • Treosulfan
  • Fludarabine
  • Busulfan
conditioning TBI/VP16Active ComparatorVP16: 60 mg/kg, 1 day TBI: 12 Gray in 6 fractions over 3 days patients > 4 years with MSD and MD
  • VP16
for mismatched donor (MMD) transplantationOtherpatients with mmd cordblood: Flu/Thio/Treo/ATG fres. or Alemtuzumab with haploidentical tx: Flu/Thio/Treo/ATG fres. or Alemtuzumab with mmd bm or pbsc:Flu/Thio/Treo or ivBU according country's decision
  • Thiotepa
  • Treosulfan
  • Fludarabine
  • Busulfan

Eligibility Criteria

        Inclusion Criteria:

        Patients with ALL (except for patients with B-ALL) who fulfil the following criteria:

          -  age at time of screening less than 18 years

          -  indication for allogeneic HSCT

          -  complete remission (CR) before HSCT

          -  written consent of the parents (legal guardian) and, if necessary, the minor patient
             via "Informed Consent Form"

          -  no pregnancy

          -  no secondary malignancy

          -  no previous HSCT

          -  HSCT is performed in a study participating centre

        Exclusion Criteria:

          -  Patients who do not fulfil the inclusion criteria

          -  Non Hodgkin-Lymphoma

          -  ALL with extramedullary involvement with indication for TBI

          -  CNS involvement at the timepoint of screening

          -  Trisomy 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
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS) Stratum 1 (randomisation TBI+ chemo-conditioning vs. chemo-conditioning only)
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:EFS (Stratum 1)
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:
Measure:Cumulative Incidence of Treatment-related mortality (TRM) for Stratum 1 and 2
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:
Measure:Cumulative Incidence of Relapse for Stratum 1 and 2
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:
Measure:acute and late toxicity for Stratum 1 and 2
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:according a preselection out of CTC3
Measure:OS (Stratum 2)
Time Frame:first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:St. Anna Kinderkrebsforschung

Trial Keywords

  • stem cell transplantation
  • children and adolescents
  • high risk acute lymphoblastic leukaemia

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