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

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ClinicalTrials.gov Identifier: NCT01949129
Recruitment Status : Recruiting
First Posted : September 24, 2013
Last Update Posted : February 17, 2016
Sponsor:
Collaborator:
ALL SCTped Forum
Information provided by (Responsible Party):
Prof. Christina Peters, St. Anna Kinderspital, Austria

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukaemia Drug: VP16 Radiation: TBI Drug: Thiotepa Drug: Treosulfan Drug: Fludarabine Drug: Busulfan Phase 2 Phase 3

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia
Study Start Date : April 2013
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2023


Arm Intervention/treatment
Experimental: conditioning Flu/Thio/Treo or Flu/Thio/ivBu
patients > 4 years with a MSD or MD
Drug: Thiotepa
2x5 mg/kg, 1 day

Drug: Treosulfan
14g/m² BS, 3 days

Drug: Fludarabine
30 mg/m² BS, 5 days

Drug: Busulfan
iV, dosage according therapeutic drug monitoring, 4 days

Active Comparator: conditioning TBI/VP16
VP16: 60 mg/kg, 1 day TBI: 12 Gray in 6 fractions over 3 days patients > 4 years with MSD and MD
Drug: VP16
60 mg/kg, administration: 1 day
Other Name: Etoposide

Radiation: TBI
12 Gy in 6 fractions over 3 days

for mismatched donor (MMD) transplantation
patients 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
Drug: Thiotepa
2x5 mg/kg, 1 day

Drug: Treosulfan
14g/m² BS, 3 days

Drug: Fludarabine
30 mg/m² BS, 5 days

Drug: Busulfan
iV, dosage according therapeutic drug monitoring, 4 days




Primary Outcome Measures :
  1. 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 ]
  2. Event free survival (EFS) Stratum 2 (mismatched donor transplantation) [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]

Secondary Outcome Measures :
  1. EFS (Stratum 1) [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
    according a preselection out of CTC3

  5. OS (Stratum 2) [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]

Other Outcome Measures:
  1. Acute Graft versus Host Disease (aGVHD) according Glucksberg Scale and Seattle Criteria [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]
  2. Secondary malignancies [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]
    Incidence, type and timepoint of occurence

  3. Chronic Graft-versus-host disease (cGvHD) according Glucksberg Scale and Seattle Criteria [ Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years ]


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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01949129


Contacts
Contact: Christina Peters, Prof. MD PhD +43140170 ext 3106 christina.peters@stanna.at
Contact: Ingeborg Hirsch, MSc +43140470 ext 4755 ingeborg.hirsch@ccri.at

  Show 100 Study Locations
Sponsors and Collaborators
St. Anna Kinderkrebsforschung
ALL SCTped Forum
Investigators
Study Chair: Christina Peters, Prof. MD PhD St. Anna Kinderspital, Vienna, Austria
Study Chair: Peter Bader, Prof. MD PhD Klinik für Kinder- u. Jugendheilkunde III, Johann Wolfgang Goethe Universität, Frankfurt, Germany
Study Chair: Franco Locatelli, Prof. MD PhD DepaDepartment of Pediatric Hematology and Oncology IRCCS Ospedale, Rome, Italy

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Christina Peters, Univ.-Prof. Dr. Christina Peters, St. Anna Kinderspital, Austria
ClinicalTrials.gov Identifier: NCT01949129     History of Changes
Other Study ID Numbers: ALL SCTped FORUM 2012
First Posted: September 24, 2013    Key Record Dates
Last Update Posted: February 17, 2016
Last Verified: February 2016

Keywords provided by Prof. Christina Peters, St. Anna Kinderspital, Austria:
stem cell transplantation
children and adolescents
high risk acute lymphoblastic leukaemia

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Treosulfan
Busulfan
Etoposide
Thiotepa
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors