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

January 12, 2024 updated by: Prof. Christina Peters, St. Anna Kinderkrebsforschung

The ALL SCTped 2012 FORUM is a multinational, multi-centre, controlled, prospective phase III study for the therapy and therapy optimisation for children and adolescents with ALL in complete morphological remission (CR, less than 5% bone marrow blasts, no blasts in cerebrospinal fluid, no other extramedullary leukemia), who have an indication for HSCT with a myeloablative conditioning regimen.

The stratification of patients in first and following remissions according to the individual transplantation modalities rests upon an indication for allogeneic HSCT and the availability of a suitable donor within the individual transplantation groups.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 is manifold: only a minority of children with ALL qualifies for allogeneic HSCT as most patients are cured with sole modern chemotherapy approaches. Those with dismal prognosis are treated in HSCT centres offering a care to patients with different diseases. Therefore it is nearly impossible to answer the complex outcome questions in single centres or even in single countries. International cooperation is essential to allow prospective investigation within comparable patient cohorts.

The trial was initiated to investigate whether chemotherapy based conditioning could replace TBI in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). It was registered and approved as a prospective, randomized, controlled, open-label, international, multicenter, phase III, non-inferiority trial. Pediatric patients with acute lymphoblastic leukemia (ALL) aged ≤18 years at diagnosis and 4-21 years at HSCT in complete remission pre-HSCT, and with an HLA-compatible related (MSD) or unrelated donor (MD) were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo). The decision to use the irradiation-free conditioning or Flu/Thio/Treo or Flu/Thio/ivBu was country specific. Patients aged < 4 years received irradiation-free conditioning. Patients with a mismatched donor (MMD) were stratified according to the donor's stem cell source (cordblood, haploidentical tx or bone marrow/peripheral blood stem cells).

The stopping rule was applied on March 31, 2019 following a suspension of random assignment in December 2018 after the chemoconditioning was proven to be significantly inferior to TBI. As a result, TBI/VP16 conditioning remains the standard for patients older than 4 years with MSD/MD, but the age limit for TBI/VP16-based conditioning may be optionally lowered to 2 years.The use of Flu/Thio/Treo or Flu/Thio/ivBu conditioning in this age group is made at centre level based on individual patient assessment. Alternatively, patients aged 0-2 years may receive Bu/VP16/Cy at the discretion of the treating physician.

The MSD/MD randomised patients remain in a follow-up to explore the impact of risk factors on the incidence of Adverse Events of Special Interest (AESIs) and on overall survival and event free survival in the entire MSD/MD cohort.

In MMD patients, event free survival (EFS) after HSCT from HLA mismatched donors using mismatched unrelated donors (MMD), mismatched cord blood or HLA haplo-identical family members is observed

Study Type

Interventional

Enrollment (Estimated)

1800

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Recruiting
        • Hospital de Pediatria "Juan P. Garrahan" Combate de Los Pozos N°1800 CABA
        • Contact:
        • Principal Investigator:
          • Raquel Staciuk, MD PhD
      • La Plata, Argentina, 1651
        • Recruiting
        • Hospital Sor Maria Ludovica, Department Hematology Stem Cell Transplant Unit
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sandra Formisano, MD PhD
        • Sub-Investigator:
          • Daniela Iglesias, MD PhD
  • Australia
      • Melbourne, Australia, 3052
        • Active, not recruiting
        • Children's Cancer Centre The Royal Children's Hospital
      • Perth, Australia, 6008
        • Active, not recruiting
        • Princess Margaret Hospital for Children
      • Randwick, Australia, 2031
        • Active, not recruiting
        • Sydney Children's Hospital
      • South Brisbane, Australia, 4101
        • Active, not recruiting
        • Lady Cilento Children's Hospital
      • Sydney, Australia, 2145
        • Active, not recruiting
        • The Children's Hospital at Westmead Oncology Unit
  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • Universitätsklinik für Kinder- und Jugendheilkunde, Abt. f. Hämato-Onkologie
        • Contact:
        • Principal Investigator:
          • Wolfgang Schwinger, MD PhD
        • Sub-Investigator:
          • Herwig Lackner, MD
      • Innsbruck, Austria, 6020
        • Recruiting
        • Universitätsklinik für Kinder- und Jugendheilkunde
        • Contact:
        • Principal Investigator:
          • Gabriele Kropshofer, MD PhD
        • Sub-Investigator:
          • Bernhard Meister, MD
      • Vienna, Austria, 1090
        • Recruiting
        • St. Anna Children's Hospital, Vienna, Austria
        • Contact:
        • Contact:
          • herbert.pichler@stanna.at
        • Principal Investigator:
          • Herbert Pichler, MD
        • Sub-Investigator:
          • Roswitha Lüftinger, MD
        • Sub-Investigator:
          • Elisabeth Salzer, MD
  • Belarus
      • Minsk, Belarus
        • Recruiting
        • Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
        • Contact:
        • Principal Investigator:
          • Nina Minakovskaya, MD
  • Belgium
      • Brussels, Belgium, 1020
        • Recruiting
        • Hopital Universitaire des Enfants Reine Fabiola (HUDERF)
        • Contact:
        • Principal Investigator:
          • Alina Ferster, MD PhD
      • Brussels, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires Saint-Luc (UCL) Hématologie et oncologie pédiatrique
        • Contact:
        • Principal Investigator:
          • Benedicte Brichard, MD PhD
      • Gent, Belgium, 9000
        • Recruiting
        • University Hospital Gent Pediatrische hemato-oncologie
        • Contact:
        • Principal Investigator:
          • Viktoria Bourdon, MD, PhD
      • Leuven, Belgium, 3000
        • Recruiting
        • University Hospitals Leuven Kinderhemato-oncologie
        • Contact:
        • Principal Investigator:
          • Marleen Renard, MD PhD
      • Liège, Belgium
        • Recruiting
        • Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
        • Contact:
        • Principal Investigator:
          • Marie Françoise Dresse, MD PhD
  • Canada
      • Calgary, Canada
        • Active, not recruiting
        • Alberta Children's Hospital Division of Pediatric Oncology
      • Montral, Canada
        • Active, not recruiting
        • Montreal Children's Hospital
      • Montreal, Canada
      • Toronto, Canada
        • Recruiting
        • Hospital for Sick Children University of Toronto Division of Haematology/Oncology
        • Contact:
        • Principal Investigator:
          • Donna Wall, MD PhD
      • Vancouver, Canada
        • Recruiting
        • BC Children's Hospital
        • Contact:
        • Principal Investigator:
          • Kirk Schultz, MD PhD
        • Sub-Investigator:
          • Jeffery Davis, MD
      • Winnipeg, Canada
        • Not yet recruiting
        • CancerCare Manitoba/University of Manitoba
        • Contact:
        • Principal Investigator:
          • Geoff Cuvelier, MD PhD
  • Chile
      • Santiago, Chile
        • Recruiting
        • Hospital Dr Luis Calvo Mackenna
        • Contact:
        • Principal Investigator:
          • Julia Palma, MD PhD
  • Croatia
      • Zagreb, Croatia
        • Recruiting
        • Department of Pediatrics, UHC Zagreb
        • Contact:
          • Ernest Bilic, MD PhD
        • Contact:
        • Principal Investigator:
          • Ernest Bilic, MD PhD
        • Sub-Investigator:
          • Toni Matic, MD PhD
  • Czechia
      • Prague, Czechia, 150 06
        • Recruiting
        • Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University
        • Contact:
        • Principal Investigator:
          • Petr Sedlacek, MD PhD
        • Sub-Investigator:
          • Petr Riha, MD
        • Sub-Investigator:
          • Renata Formankova, MD
        • Sub-Investigator:
          • Petra Keslova, MD
        • Sub-Investigator:
          • Jan Stary, MD
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Paediatric Stem Cell Transplant and Immune Deficiency, Dept. for children and adolescents 4072, Rigshospitalet
        • Contact:
        • Principal Investigator:
          • Marianne Ifversen, MD PHD
        • Sub-Investigator:
          • Carsten Heilmann, MD
  • Finland
      • Helsinki, Finland, 00029 HUS
        • Recruiting
        • Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Univ. of Helsinki
        • Contact:
        • Principal Investigator:
          • Kim Vettenranta, MD PhD
  • France
      • Bordeaux, France, 33076
        • Active, not recruiting
        • CHU Bordeaux
      • Clermont-Ferrand, France, 63003
        • Active, not recruiting
        • CHU Clermont-Ferrand
      • Grenoble, France, 38043
        • Active, not recruiting
        • CHU Grenoble - Clinique Universitaire de Pédiatrie, Hôpital Couple Enfant
      • Lille, France, 59037
        • Active, not recruiting
        • CHRU Lille, Service d'Hématologie Pédiatrique
      • Lyon, France, 69372
        • Active, not recruiting
        • IHOP / Lyon, Service Hématologie et d'Oncologie pédiatrique
      • Marseille, France, 13385
        • Active, not recruiting
        • Hopital la Timone Adulte
      • Montpellier, France, 34295
        • Active, not recruiting
        • Hôpital Arnaud de Villeneuve
      • Nancy, France, 54500
        • Active, not recruiting
        • CHU Nancy - Hôpital d'Enfants
      • Nantes, France, 44093
        • Active, not recruiting
        • CHU Nantes, Service d'onco hémato pédiatrie
      • Paris, France, 75019
        • Active, not recruiting
        • Hopital Robert Debre
      • Rennes, France, 35203
        • Active, not recruiting
        • CHU de Rennes, Serive d'Onco-Pédiatrie
      • Rouen, France, 76031
        • Active, not recruiting
        • CHU de Rouen, Hopital des Enfants, Service d' Immuno-Hématologie Oncologie Pédiatrique
      • Strasbourg, France, 67098
        • Active, not recruiting
        • CHU Strasbourg, Service d'hématologie et d'oncologie pédiatrique
  • Germany
      • Aachen, Germany, 52074
        • Active, not recruiting
        • Uniklinik RWTH Aachen, Kinder- und Jugendmedizin
      • Berlin, Germany, 13353
        • Active, not recruiting
        • Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
      • Bonn, Germany, 53113
        • Active, not recruiting
        • Universitätsklinikum Bonn, Abteilung für Pädiatrische Hämatologie und Onkologie
      • Düsseldorf, Germany, 40225
        • Active, not recruiting
        • Universitätsklinikum Düsseldorf, Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie
      • Erlangen, Germany, 1054
        • Active, not recruiting
        • Universitätsklinikum Erlangen, Kinder- und Jugendklinik
      • Essen, Germany, 45122
        • Active, not recruiting
        • Universitätsklinikum Essen, Klinik für Kinderheilkunde III
      • Frankfurt am Main, Germany, 60590
        • Active, not recruiting
        • Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Kinder- und Jugendmedizin (KKJM)
      • Freiburg, Germany, 79106
        • Active, not recruiting
        • Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin
      • Gießen, Germany, 35392
        • Active, not recruiting
        • Universitätsklinikum Gießen, Zentrum für Kinder- und Jugendmedizin
      • Greifswald, Germany, 17475
        • Active, not recruiting
        • Universitätsmedizin Greifswald, Klinik und Poliklinik für Kinder- und Jugendmedizin
      • Halle, Germany, 06120
        • Active, not recruiting
        • Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin
      • Hamburg, Germany, 20246
        • Active, not recruiting
        • Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie
      • Hannover, Germany, 30625
        • Active, not recruiting
        • Medizinische Hochschule Hannover, Zentrum Kinderheilkunde und Jugendmedizin
      • Heidelberg, Germany, 69120
        • Active, not recruiting
        • Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin
      • Jena, Germany, 07745
        • Active, not recruiting
        • Universitätsklinikum Jena, Sektion für Stammzelltransplantation
      • Kiel, Germany, 24105
        • Active, not recruiting
        • UKSH - Universitätsklinikum Schleswig-Holstein, Klinik für Allgemeine Pädiatrie
      • Leipzig, Germany, 04103
        • Active, not recruiting
        • Universitätsmedizin Leipzig, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
      • München, Germany, 80337
        • Active, not recruiting
        • Klinikum der Universität München, Dr. von Haunersches Kinderspital
      • München, Germany, 80804
        • Active, not recruiting
        • Städt. Krankenhaus München Schwabing, Universitätskinderklinik der TU München
      • Münster, Germany, 48149
        • Active, not recruiting
        • Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin
      • Regensburg, Germany, 93053
        • Active, not recruiting
        • Universitätsklinikum Regensburg, Klinik und Poliklinik für Kinder- und Jugendmedizin
      • Tübingen, Germany, 72076
        • Active, not recruiting
        • Universitätsklinik für Kinder- und Jugendmedizin Tübingen
      • Ulm, Germany, 89075
        • Active, not recruiting
        • Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin
      • Würzburg, Germany, 97080
        • Active, not recruiting
        • Universitäts-Kinderklinik Würzburg
  • Greece
      • Athens, Greece, 11527
        • Recruiting
        • Saint Sophia Children's Hospital BMT Unit
        • Sub-Investigator:
          • Anna Paisiou, MD
        • Sub-Investigator:
          • Dikaia-Eleni Ionnidou, MD
        • Sub-Investigator:
          • George Vessalas, MD
        • Contact:
        • Contact:
        • Principal Investigator:
          • Evgenios Goussetis, MD
  • Hungary
      • Budapest, Hungary, 1097
        • Recruiting
        • National Institute of Haematology and Infectious Disease, Hospital of Southern Pest, Paediatric Bone Marrow Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Gergely Krivan, MD PhD
        • Sub-Investigator:
          • Krisztián Kallay, MD PhD
  • Israel
      • Haifa, Israel, 31096
        • Recruiting
        • Rambam Medical Center
        • Contact:
        • Principal Investigator:
          • Roni Gefen, MD PhD
      • Petach-Tikva, Israel, 49202
        • Recruiting
        • Schneider Children's Medical Center of Israel
        • Contact:
        • Principal Investigator:
          • Jerry Stein, MD PhD
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Dana Children's Hospital
        • Contact:
        • Principal Investigator:
          • Ronit Elhasid, MD PhD
  • Italy
      • Bologna, Italy, 40138
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi di Bologna
        • Contact:
        • Principal Investigator:
          • Fraia Melchionda, MD
      • Florence, Italy, 50139
        • Withdrawn
        • Ospedale Mayer di Firenze SODc Tumori Pediatrici e TMO
      • Genoa, Italy, 16147
        • Not yet recruiting
        • Istituto Gaslini Genova Oncoematologia Pediatrica-
        • Contact:
        • Principal Investigator:
          • Maura Faraci, MD
      • Monza, Italy, 20900
        • Recruiting
        • A.O. San Gerardo di Monza Clinica Pediatrica
        • Contact:
        • Principal Investigator:
          • Adriana Balduzzi, MD PhD
      • Napoli, Italy, 80123
        • Not yet recruiting
        • A.O.R.N. Santobono Pausilipon, Dipartimento di Oncoematologia
        • Contact:
        • Principal Investigator:
          • Francesco Paolo Tambaro, MD
      • Padova, Italy, 35128
        • Not yet recruiting
        • Azienda Ospedaliera di Padova Oncoematologia Pediatrica
        • Contact:
        • Principal Investigator:
          • Manuela Tumino, MD
      • Pavia, Italy, 27100
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo
        • Contact:
        • Principal Investigator:
          • Mario Zecca, MD PhD
      • Pisa, Italy, 56126
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Pisana U.O. di Oncoematologia Pediatrica A.O.
        • Contact:
        • Principal Investigator:
          • Gabriella Casazza, MD PhD
      • Rome, Italy, 00165
        • Recruiting
        • Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome
        • Contact:
        • Principal Investigator:
          • Franco Locatelli, MD PhD
      • Torino, Italy, 10126
        • Terminated
        • Ospedale Infantile Regina Margherita SC Oncoematologia e Centro Trapianti
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Recruiting
        • University of Malaya, Department of Paediatrics
        • Contact:
        • Principal Investigator:
          • Hany Ariffin, MD PhD
  • Mexico
      • Ciudad de México, Mexico
        • Recruiting
        • Instituto Nacional de Peditria
        • Contact:
        • Principal Investigator:
          • Alberto Olaya Vargas, MD PhD
  • Netherlands
      • Leiden, Netherlands, 2300
        • Recruiting
        • Leiden University Medical Center Department of Pediatrics/BMT unit
        • Contact:
          • Arjan Lankester, MD PhD
        • Contact:
        • Principal Investigator:
          • Arjan Lankester, MD PhD
      • Utrecht, Netherlands, 3584
        • Recruiting
        • Princess Máxima Center for Pediatric Oncology
        • Contact:
        • Principal Investigator:
          • Marc Bierings, MD PhD
  • New Zealand
      • Auckland, New Zealand, 1142
        • Active, not recruiting
        • Starship Children's Hospital
  • Norway
      • Oslo, Norway, 0424
        • Recruiting
        • Oslo University Hospital Rikshospitalet
        • Contact:
        • Principal Investigator:
          • Jochen Büchner, MD PhD
  • Poland
      • Bydgoszcz, Poland
        • Recruiting
        • University Hospital No.1, Collegium Medicum UMK, department of Paediatrics, Oncology, Hematology and Paediatric Transplantology
        • Contact:
        • Principal Investigator:
          • Mariusz Wysocki, MD PhD
      • Kraków, Poland
        • Withdrawn
        • University Children's Hospital in Krakow, Department of Transplantation
      • Lublin, Poland
        • Not yet recruiting
        • Children's University Hospital, Dept. Pediatric Hematology, Oncology, and Transplantology
        • Contact:
        • Principal Investigator:
          • Jerzy R. Kowalczyk, MD
      • Poznań, Poland
        • Recruiting
        • Poznan University of Medical Sciences, Department of Pediatric Onology, Hematology & HSCT
        • Contact:
        • Principal Investigator:
          • Jacek Wachowiak, MD PhD
      • Wrocław, Poland
        • Recruiting
        • Cape of Hope, Wroclaw Medical University
        • Contact:
        • Principal Investigator:
          • Alicja Chybicka, MD PhD
  • Romania
      • Bukarest, Romania
        • Recruiting
        • IInsitutul Clinic Fundeni, Sectia de Transplant Medular
        • Contact:
        • Principal Investigator:
          • Anca Colita, MD PhD
      • Timişoara, Romania
        • Recruiting
        • University of Medicine and Pharmacy V. BABES, Emergency Children's Hospital LOUIS TURCANU, III. Clinic of Pediatrics , Department of Onco-hematology and Bone Marrow Transplantation
        • Contact:
        • Principal Investigator:
          • Cristian Jinca, MD PhD
  • Saudi Arabia
      • Riyadh, Saudi Arabia
        • Recruiting
        • King Abdullah specialists children hospital
        • Contact:
        • Principal Investigator:
          • Mohammed Essa, MD PhD
  • Slovakia
      • Bratislava, Slovakia, 83340
        • Recruiting
        • University Children's Hospital
        • Contact:
        • Principal Investigator:
          • Peter Svec, MD PhD
        • Sub-Investigator:
          • Dominika Tanuskova, MD
  • Slovenia
      • Ljubljana, Slovenia
        • Recruiting
        • University childrens' hospital, UMCL
        • Contact:
        • Principal Investigator:
          • Simona Avčin, MD
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Santa Creu i Sant Pau
        • Contact:
        • Principal Investigator:
          • Isabel Badell, MD
      • Barcelona, Spain
        • Recruiting
        • Hospital Vall d'Hebron
        • Contact:
        • Principal Investigator:
          • Cristina Díaz de Heredia, MD
      • Murcia, Spain
        • Recruiting
        • Hospital Virgen de la Arrixaca
        • Contact:
        • Principal Investigator:
          • José Luis Fuster, MD
      • Málaga, Spain
      • Oviedo, Spain
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
        • Principal Investigator:
          • Pilar Palomo, MD
  • Sweden
      • Göteborg, Sweden, 41685
        • Recruiting
        • Queen Silvia Children's Hospital, Department of Pediatric Oncology (Avdelnig 321-322)
        • Contact:
        • Principal Investigator:
          • Cecilia Langenskiöld, MD
      • Lund, Sweden, 22185
        • Recruiting
        • Skane University Hospital, Dept. of Pediatrics, Section for Hematology and Oncology
        • Contact:
        • Principal Investigator:
          • Dominik Turkiewicz, MD
      • Stockholm, Sweden, 14186
        • Recruiting
        • Karolinska University Hospital, Department of Pediatrics
        • Contact:
        • Principal Investigator:
          • Jacek Toporski, MD
      • Uppsala, Sweden, 75185
        • Recruiting
        • University Children's Hospital, Dept. of Women's & Children's Health Section for Pediatrics
        • Contact:
        • Principal Investigator:
          • Natalja Jackman, MD PhD
  • Switzerland
      • Basel, Switzerland, 4056
        • Recruiting
        • Universitäts-Kinderspital beider Basel (UKBB)
        • Contact:
        • Principal Investigator:
          • Nicolas Von der Weid, MD PhD
      • Geneva, Switzerland, 1211
        • Recruiting
        • HUG Hôpitaux Universitaire de Genève
        • Contact:
        • Principal Investigator:
          • Marc Ansari, MD PhD
      • Zurich, Switzerland, 8032
        • Recruiting
        • Universitäts-Kinderspital Zürich
        • Contact:
        • Principal Investigator:
          • Güngör Tayfun, MD PhD
  • Turkey
      • Ankara, Turkey, 06100
        • Recruiting
        • Ankara University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
          • Mehmet Ertem, MD PhD
        • Contact:
        • Principal Investigator:
          • Mehmet Ertem, MD PhD
        • Sub-Investigator:
          • Elif Ince, MD
      • Ankara, Turkey
        • Recruiting
        • Gazi University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Ulker Kocak, MD PhD
      • Ankara, Turkey
        • Recruiting
        • Gulhane Training and Research Hospital
        • Contact:
        • Principal Investigator:
          • Orhan Gursel, MD PhD
      • Antalya, Turkey
        • Recruiting
        • Akdeniz University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Alphan Kupesiz, MD PhD
      • Antalya, Turkey
        • Recruiting
        • Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Akif Yesilipek, MD PhD
      • Istanbul, Turkey
        • Recruiting
        • Acibadem University Atakent Hospital Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Gulyuz Ozturk, MD PhD
        • Sub-Investigator:
          • Didem Atay, MD
      • Istanbul, Turkey
        • Recruiting
        • Bahcelievler Medicalpark Hospital Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Tunc Fisgin, MD PhD
      • Istanbul, Turkey
        • Recruiting
        • Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Gulsun Karasu, MD PhD
        • Sub-Investigator:
          • Suar Kilic, MD
      • Istanbul, Turkey
        • Recruiting
        • Medipol Mega Universite Hastanesi
        • Contact:
        • Principal Investigator:
          • Sema Anak, MD PhD
        • Sub-Investigator:
          • Yöntem Yaman, MD
      • Izmir, Turkey
        • Recruiting
        • Dokuzeylul University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Hale Oren, MD PhD
        • Sub-Investigator:
          • Sebnem Yilmaz, MD
      • Izmir, Turkey
        • Recruiting
        • Ege University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Savaş Kansoy, MD PhD
        • Sub-Investigator:
          • Serap Aksoylar, MD
      • Kayseri, Turkey
        • Recruiting
        • Erciyes University School of Medicine Pediatric Stem Cell Transplantation Unit
        • Contact:
        • Principal Investigator:
          • Musa Karakukcu, MD PhD
        • Sub-Investigator:
          • Ekrem Unal, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

  • age at diagnosis ≤ 18 years. Age at HSCT ≤ 21 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Flu/Thio/Treo

Fludarabine/Thiotepa/Treosulfan is used as conditioning regimen for haematopoietic stem cell transplantation (HSCT) in patients with:

  • MSD (matched sibling donors) or MD (matched related or unrelated donors). In addition, patients undergoing MD HSCT will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) with CB (Cord blood) or TCD (T-Cell depletion) or CD34+ selection. In addition, these patients will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) patients receiving Post TX-Cyclophosphamide
Drug: Thiotepa
2x5 mg/kg BW, 1 day
Other Names:
  • Thio
Drug: Treosulfan
14g/m² BS, 3 days
Other Names:
  • Treo
Drug: Fludarabine
30 mg/m² BS, 5 days
Other Names:
  • Flu
Drug: ATG Thymoglobulin
MD: ATG Thymo: 2,5mg/kg BW/d 3 days.
Other Names:
  • ATG Thymo
Drug: Grafalon
MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days
Other Names:
  • Anti-human T-lymphocyte immunoglobulin
Active Comparator: TBI/VP16

TBI (Total Body Irradiation) / VP16 is used as conditioning regimen for haematopoietic stem cell transplantation (HSCT) in patients older than 48 months with:

  • MSD (matched sibling donors) or MD (matched related or unrelated donors). In addition, patients undergoing MD HSCT will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) with CB (Cord blood) or TCD (T-Cell depletion) or CD34+ selection. In addition, these patients will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) patients receiving Post TX-Cyclophosphamide.

Patients aged 24-48 months may optionally receive Total Body Irradiation (TBI).
Drug: ATG Thymoglobulin
MD: ATG Thymo: 2,5mg/kg BW/d 3 days.
Other Names:
  • ATG Thymo
Drug: Grafalon
MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days
Other Names:
  • Anti-human T-lymphocyte immunoglobulin
Radiation: TBI
2 x 2Gy/day , 3 days (total 12Gy)
Drug: VP16
60 mg/kg BW,1 day in TBI/VP16 conditioning; 40 mg/kg BW in Bu/VP16/Cy conditioning
Other Names:
  • Etoposide
Experimental: Flu/Thio/ivBu

Fludarabine/Thiotepa/iV Busulfan is used as conditioning regimen for haematopoietic stem cell transplantation (HSCT) in patients with:

  • MSD (matched sibling donors) or MD (matched related or unrelated donors). In addition, patients undergoing MD HSCT will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) with CB (Cord blood) or TCD (T-Cell depletion) or CD34+ selection. In addition, these patients will receive ATG Thymo- or Grafalon.
  • MMD (mismatched donors) patients receiving Post TX-Cyclophosphamide
Drug: Thiotepa
2x5 mg/kg BW, 1 day
Other Names:
  • Thio
Drug: Fludarabine
30 mg/m² BS, 5 days
Other Names:
  • Flu
Drug: ATG Thymoglobulin
MD: ATG Thymo: 2,5mg/kg BW/d 3 days.
Other Names:
  • ATG Thymo
Drug: Grafalon
MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days
Other Names:
  • Anti-human T-lymphocyte immunoglobulin
Drug: Busulfan
iV, dosage according therapeutic drug monitoring, 4 days
Other Names:
  • Bu
Drug: Cyclophosphamide
as part of conditioning 60 mg/kg BW 2 days or as GvHD Prophylaxis 50mg/kg BW/d 2 days with Mesna
Other Names:
  • Cy
Experimental: Bu/VP16/Cy
Busulfan/VP16/Cyclophosphamide is an alternative conditioning arm that may optionally be used for HSCT with MSD/MD and MMD graft in patients aged 0-24 months. Patients undergoing MD HSCT will also receive ATG Thymo- or Grafalon.
Drug: Busulfan
iV, dosage according therapeutic drug monitoring, 4 days
Other Names:
  • Bu
Drug: VP16
60 mg/kg BW,1 day in TBI/VP16 conditioning; 40 mg/kg BW in Bu/VP16/Cy conditioning
Other Names:
  • Etoposide
Drug: Cyclophosphamide
as part of conditioning 60 mg/kg BW 2 days or as GvHD Prophylaxis 50mg/kg BW/d 2 days with Mesna
Other Names:
  • Cy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) Stratum 1a (randomisation TBI+ chemo-conditioning vs. chemo-conditioning only)
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Stratum 1 - randomisation related question was closed in December 2018; patients are in active follow-up: To show 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). The primary endpoint is the OS calculated from the date of the randomisation. Death from any cause will be considered an event.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
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
EFS after allogeneic HSCT. EFS calculated from date of recruitment to disease progression or relapse, secondary neoplasm and death from any cause.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Overall Survival (OS), Stratum 1b: MSD/MD without randomisation
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
To explore the impact of risk factors on the incidence of adverse events of special interest (AESIs) and on overall survival and event free survival in the entire MSD/MD cohort
first: 18 months after inclusion of first patient, afterwards annually up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EFS (Stratum 1a and 1b)
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
EFS calculated from date of randomization (1a) or recruitment (1b) to disease progression or relapse, secondary neoplasm and death from any cause. Patients lost to follow-up without event will be censored at the date of their last follow-up evaluation.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
TRM
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Cumulative Incidence of Treatment-related mortality (TRM) for Stratum 1 and 2.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Relapse/progression
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Cumulative Incidence of Relapse for Stratum 1a, 1b and 2.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Acute and late toxicity for Stratum 1a, 1b and 2
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
according a preselection out of CTC3
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
OS (Stratum 2)
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
The primary endpoint is the OS calculated from the date of the recruitment . Death from any cause will be considered an event.
first: 18 months after inclusion of first patient, afterwards annually up to 10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Graft versus Host Disease (aGVHD)
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
According to the modified Seattle Glucksberg criteria
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Secondary malignancies
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Incidence, type and timepoint of occurence
first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Chronic Graft-versus-host disease (cGvHD)
Time Frame: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Chronic GVHD is diagnosed using criteria created through the NIH consensus development project
first: 18 months after inclusion of first patient, afterwards annually up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Anna Kinderkrebsforschung

Collaborators

Assistance Publique - Hôpitaux de Paris
Australian & New Zealand Children's Haematology/Oncology Group
European Society for Blood and Marrow Transplantation
Swiss Pediatric Oncology Group
ALL SCTped Forum
ALL-BFM Study Group
Dutch Childhood Oncology Group

Investigators

  • Study Chair: Christina Peters, Prof. MD PhD, St. Anna Kinderspital, Vienna, Austria
  • Study Chair: Peter Bader, Prof. MD PhD, Goethe University
  • Study Chair: Franco Locatelli, Prof. MD PhD, Ospedale Pediatrico Bambino Gesù, Rome, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

April 1, 2030

Study Registration Dates

First Submitted

September 9, 2013

First Submitted That Met QC Criteria

September 19, 2013

First Posted (Estimated)

September 24, 2013

Study Record Updates

Last Update Posted (Actual)

January 16, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALL SCTped FORUM 2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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