Acute Lymphoblastic LeukaemiaPhase 2/3NCT01949129
Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia
A Phase 2/3 study testing VP16, TBI and Thiotepa in people with Acute Lymphoblastic Leukaemia, run by St. Anna Kinderkrebsforschung at 119 sites in 31 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukaemia
- What is being tested?
- VP16, TBI and Thiotepa
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,800 participants
- Where
- 119 sitesin 31 countries
- Study dates
- Apr 2013to 1 Jun 2030
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 9Show fewer
- no secondary malignancy
- no previous HSCT
- HSCT is performed in a study participating centre
Who cannot join
- 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
Trial locations and contacts
119 sites in 31 countries. Contact the study team or a site near you to ask about taking part.
119 sites in 31 countries
Germany24 sites
- Active, not recruiting
Uniklinik RWTH Aachen, Kinder- und Jugendmedizin
Aachen, 52074
- Active, not recruiting
Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
Berlin, 13353
- Active, not recruiting
Universitätsklinikum Bonn, Abteilung für Pädiatrische Hämatologie und Onkologie
Bonn, 53113
- Active, not recruiting
Universitätsklinikum Düsseldorf, Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie
Düsseldorf, 40225
- Active, not recruiting
Universitätsklinikum Erlangen, Kinder- und Jugendklinik
Erlangen, 1054
- Active, not recruiting
Universitätsklinikum Essen, Klinik für Kinderheilkunde III
Essen, 45122
- Active, not recruiting
Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Kinder- und Jugendmedizin (KKJM)
Frankfurt am Main, 60590
- Active, not recruiting
Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin
Freiburg im Breisgau, 79106
- Active, not recruiting
Universitätsklinikum Gießen, Zentrum für Kinder- und Jugendmedizin
Giessen, Gießen, 35392
- Active, not recruiting
Universitätsmedizin Greifswald, Klinik und Poliklinik für Kinder- und Jugendmedizin
Greifswald, 17475
- Active, not recruiting
Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin
Halle, 06120
- Active, not recruiting
Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie
Hamburg, 20246
- Active, not recruiting
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde und Jugendmedizin
Hanover, 30625
- Active, not recruiting
Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin
Heidelberg, 69120
- Active, not recruiting
Universitätsklinikum Jena, Sektion für Stammzelltransplantation
Jena, 07745
- Active, not recruiting
UKSH - Universitätsklinikum Schleswig-Holstein, Klinik für Allgemeine Pädiatrie
Kiel, 24105
- Active, not recruiting
Universitätsmedizin Leipzig, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
Leipzig, 04103
- Active, not recruiting
Klinikum der Universität München, Dr. von Haunersches Kinderspital
München, 80337
- Active, not recruiting
Städt. Krankenhaus München Schwabing, Universitätskinderklinik der TU München
München, 80804
- Active, not recruiting
Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin
Münster, 48149
- Active, not recruiting
Universitätsklinikum Regensburg, Klinik und Poliklinik für Kinder- und Jugendmedizin
Regensburg, 93053
- Active, not recruiting
Universitätsklinik für Kinder- und Jugendmedizin Tübingen
Tübingen, 72076
- Active, not recruiting
Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin
Ulm, 89075
- Active, not recruiting
Universitäts-Kinderklinik Würzburg
Würzburg, 97080
France13 sites
- Active, not recruiting
CHU Bordeaux
Bordeaux, 33076
- Active, not recruiting
CHU Clermont-Ferrand
Clermont-Ferrand, 63003
- Active, not recruiting
CHU Grenoble - Clinique Universitaire de Pédiatrie, Hôpital Couple Enfant
Grenoble, 38043
- Active, not recruiting
CHRU Lille, Service d'Hématologie Pédiatrique
Lille, 59037
- Active, not recruiting
IHOP / Lyon, Service Hématologie et d'Oncologie pédiatrique
Lyon, 69372
- Active, not recruiting
Hopital la Timone Adulte
Marseille, 13385
- Active, not recruiting
Hopital Arnaud de Villeneuve
Montpellier, 34295
- Active, not recruiting
CHU Nancy - Hopital d'Enfants
Nancy, 54500
- Active, not recruiting
CHU Nantes, Service d'onco hémato pédiatrie
Nantes, 44093
- Active, not recruiting
Hôpital Robert Debré
Paris, 75019
- Active, not recruiting
CHU de Rennes, Serive d'Onco-Pédiatrie
Rennes, 35203
- Active, not recruiting
CHU de Rouen, Hopital des Enfants, Service d' Immuno-Hématologie Oncologie Pédiatrique
Rouen, 76031
- Active, not recruiting
CHU Strasbourg, Service d'hématologie et d'oncologie pédiatrique
Strasbourg, 67098
Turkey (Türkiye)12 sites
- Active, not recruiting
Ankara University School of Medicine Pediatric Stem Cell Transplantation Unit
Ankara, 06100
- Active, not recruiting
Gazi University School of Medicine Pediatric Stem Cell Transplantation Unit
Ankara
- Active, not recruiting
Gülhane Training and Research Hospital
Ankara
- Active, not recruiting
Akdeniz University School of Medicine Pediatric Stem Cell Transplantation Unit
Antalya
- Active, not recruiting
Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit
Antalya
- Active, not recruiting
Acibadem University Atakent Hospital Pediatric Stem Cell Transplantation Unit
Istanbul
- Active, not recruiting
Bahcelievler Medicalpark Hospital Pediatric Stem Cell Transplantation Unit
Istanbul
- Active, not recruiting
Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit
Istanbul
- Active, not recruiting
Medipol Mega Üniversite Hastanesi
Istanbul
- Active, not recruiting
Dokuzeylul University School of Medicine Pediatric Stem Cell Transplantation Unit
Izmir
- Active, not recruiting
Ege University School of Medicine Pediatric Stem Cell Transplantation Unit
Izmir
- Active, not recruiting
Erciyes University School of Medicine Pediatric Stem Cell Transplantation Unit
Kayseri
Italy10 sites
- Withdrawn
Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi di Bologna
Bologna, 40138
- Withdrawn
Ospedale Mayer di Firenze SODc Tumori Pediatrici e TMO
Florence, 50139
- Withdrawn
Istituto Gaslini Genova Oncoematologia Pediatrica-
Genoa, 16147
- Active, not recruiting
A.O. San Gerardo di Monza Clinica Pediatrica
Monza, 20900
- Withdrawn
A.O.R.N. Santobono Pausilipon, Dipartimento di Oncoematologia
Naples, 80123
- Withdrawn
Azienda Ospedaliera di Padova Oncoematologia Pediatrica
Padova, 35128
- Active, not recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
- Withdrawn
Azienda Ospedaliero Universitaria Pisana U.O. di Oncoematologia Pediatrica A.O.
Pisa, 56126
- Active, not recruiting
Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome
Rome, 00165
- Terminated
Ospedale Infantile Regina Margherita SC Oncoematologia e Centro Trapianti
Torino, 10126
Canada6 sites
- Active, not recruiting
Alberta Children's Hospital Division of Pediatric Oncology
Calgary
- Active, not recruiting
Montreal Children's Hospital
Montral
- Active, not recruiting
CHU Sainte-Justine Hematology-Oncology Division
Montreal
- Completed
Hospital for Sick Children University of Toronto Division of Haematology/Oncology
Toronto
- Completed
BC Children's Hospital
Vancouver
- Withdrawn
CancerCare Manitoba/University of Manitoba
Winnipeg
Australia5 sites
- Active, not recruiting
Children's Cancer Centre The Royal Children's Hospital
Melbourne, 3052
- Active, not recruiting
Princess Margaret Hospital for Children
Perth, 6008
- Active, not recruiting
Sydney Children's Hospital
Randwick, 2031
- Active, not recruiting
Lady Cilento Children's Hospital
South Brisbane, 4101
- Active, not recruiting
The Children's Hospital at Westmead Oncology Unit
Sydney, 2145
Belgium5 sites, 5 recruiting
- Recruiting
Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)
Brussels, 1020
Pauline Mazilier, MD
Pauline Mazilier, MD
- Recruiting
Cliniques Universitaires Saint-Luc (UCL) Hématologie et oncologie pédiatrique
Brussels, 1200
Benedicte Brichard, MD PhD, benedicte.brichard@uclouvain.be
Benedicte Brichard, MD PhD
- Recruiting
University Hospital Gent Pediatrische hemato-oncologie
Ghent, 9000
Viktoria Bourdon, MD, PhD, vicotria.bordon@uzgent.be
Viktoria Bourdon, MD, PhD
- Recruiting
University Hospitals Leuven Kinderhemato-oncologie
Leuven, 3000
Marleen Renard, MD PhD, marleen.renard@uzleuven.be
Marleen Renard, MD PhD
- Recruiting
Centre Hospitalier Universitaire de Liège Domaine Universitaire du Sart Tilman
Liège
Marie Françoise Dresse, MD PhD, marie.francoise.dresse@chrcitadelle.be
Marie Françoise Dresse, MD PhD
Poland5 sites
- Active, not recruiting
University Hospital No.1, Collegium Medicum UMK, department of Paediatrics, Oncology, Hematology and Paediatric Transplantology
Bydgoszcz
- Withdrawn
University Children's Hospital in Krakow, Department of Transplantation
Krakow
- Active, not recruiting
Children's University Hospital, Dept. Pediatric Hematology, Oncology, and Transplantology
Lublin
- Active, not recruiting
Poznan University of Medical Sciences, Department of Pediatric Onology, Hematology & HSCT
Poznan
- Active, not recruiting
Cape of Hope, Wroclaw Medical University
Wroclaw
Spain5 sites, 4 recruiting
- Recruiting
Hospital Santa Creu i Sant Pau
Barcelona
Iván López Torija, MD, ilopezt@santpau.cat
Iván López Torija, MD
- Recruiting
Hospital Vall d'Hebron
Barcelona
Cristina Díaz de Heredia, MD, cristina.diazdeheredia@vallhebron.cat
Cristina Díaz de Heredia, MD
- Withdrawn
Hospital Materno Infantil de Málaga
Málaga
- Recruiting
Hospital Virgen de la Arrixaca
Murcia
José Luis Fuster, MD, josel.fuster@carm.es
José Luis Fuster, MD
- Recruiting
Hospital Universitario Central de Asturias
Oviedo
Pilar Palomo, MD, pilarpalomo@gmail.com
Pilar Palomo, MD
Sweden4 sites, 4 recruiting
- Recruiting
Queen Silvia Children's Hospital, Department of Pediatric Oncology (Avdelnig 321-322)
Gothenburg, 41685
Cecilia Langenskiöld, MD, cecilia.langenskiold@vgregion.se
Cecilia Langenskiöld, MD
- Recruiting
Skane University Hospital, Dept. of Pediatrics, Section for Hematology and Oncology
Lund, 22185
Dominik Turkiewicz, MD, dominik.turkiewicz@skane.se
Dominik Turkiewicz, MD
- Recruiting
Karolinska University Hospital, Department of Pediatrics
Stockholm, 14186
Jacek Toporski, MD, jacek.toporski@regionstockholm.se
Jacek Toporski, MD
- Recruiting
University Children's Hospital, Dept. of Women's & Children's Health Section for Pediatrics
Uppsala, 75185
Natalja Jackman, MD PhD, natalja.jackman@akademiska.se
Natalja Jackman, MD PhD
Austria3 sites, 3 recruiting
- Recruiting
Universitätsklinik für Kinder- und Jugendheilkunde, Abt. f. Hämato-Onkologie
Graz, 8036
Wolfgang Schwinger, MD PhD, wolfgang.schwinger@medunigraz.at
Wolfgang Schwinger, MD PhD
- Recruiting
Universitätsklinik für Kinder- und Jugendheilkunde
Innsbruck, 6020
Gabriele Kropshofer, MD PhD, gabriele.kropshofer@tirol-kliniken.at
Gabriele Kropshofer, MD PhD
- Recruiting
St. Anna Children's Hospital, Vienna, Austria
Vienna, 1090
Herbert Pichler, MD, herbert.pichler@stanna.at
herbert.pichler@stanna.at
Israel3 sites
- Active, not recruiting
Rambam Medical Center
Haifa, 31096
- Active, not recruiting
Schneider Children's Medical Center of Israel
Petah Tikva, 49202
- Active, not recruiting
Dana Children's Hospital
Tel Aviv, 64239
Switzerland3 sites, 3 recruiting
- Recruiting
Universitäts-Kinderspital beider Basel (UKBB)
Basel, 4056
Tamara Diesch, MD PhD, tamara.diesch-furlanetto@ukbb.ch
Tamara Diesch, MD PhD
- Recruiting
HUG Hôpitaux Universitaire de Genève
Geneva, 1211
Marc Ansari, MD PhD, Marc.Ansari@hcuge.ch
Marc Ansari, MD PhD
- Recruiting
Universitäts-Kinderspital Zurich
Zurich, 8032
Güngör Tayfun, MD PhD, tayfun.guengoer@kispi.uzh.ch
Güngör Tayfun, MD PhD
Argentina2 sites, 2 recruiting
- Recruiting
Hospital de Pediatria "Juan P. Garrahan" Combate de Los Pozos N°1800 CABA
Buenos Aires
Raquel Staciuk, MD PhD, rstaciuk@gmail.com
Raquel Staciuk, MD PhD
- Recruiting
Hospital Sor Maria Ludovica, Department Hematology Stem Cell Transplant Unit
La Plata, 1651
Sandra Formisano, MD, sandraformisano@yahoo.com.ar
Sandra Formisano, MD PhD
Netherlands2 sites, 1 recruiting
- Completed
Leiden University Medical Center Department of Pediatrics/BMT unit
Leiden, 2300
- Recruiting
Princess Máxima Center for Pediatric Oncology
Utrecht, 3584
Friso Calkoen, MD, F.G.J.Calkoen-2@prinsesmaximacentrum.nl
Friso Calkoen, MD
Romania2 sites
- Active, not recruiting
IInsitutul Clinic Fundeni, Sectia de Transplant Medular
Bucharest
- Completed
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
Timișoara
Belarus1 site
- Active, not recruiting
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Minsk
Chile1 site, 1 recruiting
- Recruiting
Hospital Dr Luis Calvo Mackenna
Santiago
Julia Palma, MD PhD, jpalmab@vtr.net
Julia Palma, MD PhD
Croatia1 site, 1 recruiting
- Recruiting
Department of Pediatrics, UHC Zagreb
Zagreb
Ernest Bilic, MD PhD, ernest.bilic@kbc-zagreb.hr
Zrinko Salek, MD, zsalek@kbc-zagreb.hr
Czechia1 site, 1 recruiting
- Recruiting
Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University
Prague, 150 06
Petr Riha, MD PhD, petr.riha@fnmotol.cz
Petr Riha, MD
Denmark1 site, 1 recruiting
- Recruiting
Paediatric Stem Cell Transplant and Immune Deficiency, Dept. for children and adolescents 4072, Rigshospitalet
Copenhagen, 2100
Marianne Ifversen, MD PhD, ifversen@rh.regionh.dk
Marianne Ifversen, MD PHD
Finland1 site
- Completed
Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Univ. of Helsinki
Helsinki, 00029 HUS
Greece1 site, 1 recruiting
- Recruiting
Saint Sophia Children's Hospital BMT Unit
Athens, 11527
Evgenios Goussetis, MD, evgoussetis@gmail.com
Dikaia Eleni Ioannidou, MD, elda.ioannidou@gmail.com
Hungary1 site, 1 recruiting
- Recruiting
National Institute of Haematology and Infectious Disease, Hospital of Southern Pest, Paediatric Bone Marrow Transplantation Unit
Budapest, 1097
Gergely Krivan, MD PhD, krivang@hu.inter.net
Gergely Krivan, MD PhD
Malaysia1 site, 1 recruiting
- Recruiting
University of Malaya, Department of Paediatrics
Kuala Lumpur
Hany Ariffin, MD PhD, hany@ummc.edu.my
Hany Ariffin, MD PhD
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Peditria
Mexico City
Alberto Olaya Vargas, MD PhD, alberto.olaya@yahoo.com.mx
Alberto Olaya Vargas, MD PhD
New Zealand1 site
- Active, not recruiting
Starship Children's Hospital
Auckland, 1142
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital Rikshospitalet
Oslo, 0424
Jochen Büchner, MD PhD, jocbuc@ous-hf.no
Jochen Büchner, MD PhD
Saudi Arabia1 site, 1 recruiting
- Recruiting
King Abdullah specialists children hospital
Riyadh
Mohammed Essa, MD PhD, essamo@mngha.med.sa
Mohammed Essa, MD PhD
Slovakia1 site, 1 recruiting
- Recruiting
University Children's Hospital
Bratislava, 83340
Peter Svec, MD PhD, peter.svec@gmail.com
Peter Svec, MD PhD
Slovenia1 site, 1 recruiting
- Recruiting
University childrens' hospital, UMCL
Ljubljana
Simona Avčin, MD, simona.avcin@kclj.si
Simona Avčin, MD
About this study
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.
Read the 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 as a prospective, randomised, global study 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 (cord blood, haploidentical HSCT 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. If TBI/VP16 was not the conditioning regimen, participating centres/treating physicians could choose either Flu/Thio/iv BU or Flu/Thio/Treo based on individual patient assessment.
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.
During the trial, new questions arise, such as new chemotherapy options for no-irradiation conditioning, individualised drug dosing, influence of pharmacogenomics, immune reconstitution, influence of different levels of MRD negativity, donor factors such as MSD vs. MD, HSCT in patients younger than 4 years and in infants, differences in outcome in a non-randomised cohort, factors influencing the development of acute and chronic GvHD, and many other questions that could be analysed and investigated based on the data collected in the trial. In addition, relapse remains the major cause of treatment failure in infants and young children with high-risk ALL undergoing HSCT.
To address this, the protocol was amended (version 7.0/29 October 2022) to allow a choice of conditioning between TBI/VP16 and chemo-conditioning Flu/Thio/Treo or Flu/Thio/Bu and optionally Bu/VP16/Cy for patients aged 0-2 years.
- TBI/VP16 remains the standard of care for patients > 4 years.
- Patients aged 2-4 years may optionally receive the TBI/VP16 conditioning at the discretion of the treating physician to avoid acute and long-term side effects, which are more pronounced in this age group.
- Patients <2 years of age do not receive TBI.
- For patients who are not eligible for TBI, treating physicians may choose either Flu/Thio/ivBu or Flu/Thio/Treo as both chemo-conditioning regimens result in similar OS, EFS and NRM.
- Patients aged 0-2 years may receive Bu/VP16/Cy at the discretion of the treating physician.
In countries that have stopped enrolling patients prior to the approval of protocol version 7.0/29 October 2022, or in countries where V7.0 was not approved at the time of the transition to the Clinical Trials Regulation, the choice of conditioning between TBI/VP16 and chemo-conditioning according to international protocol version 6.0/9 September 2019 is as follows:
- TBI/VP16 remains the standard of care for patients > 4 years.
- Patients <4 years of age do not receive TBI.
- For patients aged <4 years and those ineligible for TBI, treating physicians may choose either Flu/Thio/ivBu or Flu/Thio/Treo as both chemo-conditioning regimens result in similar OS, EFS and NRM.
In EU/EEA countries that have transitioned to the Clinical Trials Regulation, a consolidated version of the protocol (v8.0, effective 1 July 2024) is in use, reflecting the common core provisions of versions 6 and 7 that have been approved in the respective Member States.
Countries that are not subject to the CTR use versions that have been approved in their respective countries.
- Conditions
- Acute Lymphoblastic Leukaemia
- Being tested
- VP16, TBI, Thiotepa, Treosulfan, Fludarabine
- Keywords
- stem cell transplantation, children and adolescents, high risk acute lymphoblastic leukaemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VP16Drug
Also called Etoposide
60 mg/kg BW,1 day in TBI/VP16 conditioning; 40 mg/kg BW in Bu/VP16/Cy conditioning
TBIRadiation
2 x 2Gy/day , 3 days (total 12Gy)
ThiotepaDrug
Also called Thio
2x5 mg/kg BW, 1 day
TreosulfanDrug
Also called Treo
14g/m² BS, 3 days
FludarabineDrug
Also called Flu
30 mg/m² BS, 5 days
BusulfanDrug
Also called Bu
iV, dosage according therapeutic drug monitoring, 4 days
ATG ThymoglobulinDrug
Also called ATG Thymo
MD: ATG Thymo: 2,5mg/kg BW/d 3 days.
CyclophosphamideDrug
Also called Cy
as part of conditioning 60 mg/kg BW 2 days or as GvHD Prophylaxis 50mg/kg BW/d 2 days with Mesna
GrafalonDrug
Also called Anti-human T-lymphocyte immunoglobulin
MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days
| Study group | Role | What they receive |
|---|---|---|
| Flu/Thio/Treo | Experimental | 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 Receives: Drug: Thiotepa; Drug: Treosulfan; Drug: Fludarabine; Drug: ATG Thymoglobulin; Drug: Grafalon |
| TBI/VP16 | Active comparator | 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). Receives: Drug: VP16; Radiation: TBI; Drug: ATG Thymoglobulin; Drug: Grafalon |
| Flu/Thio/ivBu | Experimental | 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 Receives: Drug: Thiotepa; Drug: Fludarabine; Drug: Busulfan; Drug: ATG Thymoglobulin; Drug: Cyclophosphamide; Drug: Grafalon |
| Bu/VP16/Cy | Experimental | 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. Receives: Drug: VP16; Drug: Busulfan; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) Stratum 1a (randomisation TBI+ chemo-conditioning vs. chemo-conditioning only)
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.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Event free survival (EFS) Stratum 2 (mismatched donor transplantation)
EFS after allogeneic HSCT. EFS calculated from date of recruitment to disease progression or relapse, secondary neoplasm and death from any cause.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Overall Survival (OS), Stratum 1b: MSD/MD without randomisation
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
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Secondary outcomes (5)
EFS (Stratum 1a and 1b)
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.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
TRM
Cumulative Incidence of Treatment-related mortality (TRM) for Stratum 1 and 2.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Relapse/progression
Cumulative Incidence of Relapse for Stratum 1a, 1b and 2.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Acute and late toxicity for Stratum 1a, 1b and 2
according a preselection out of CTC3
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
OS (Stratum 2)
The primary endpoint is the OS calculated from the date of the recruitment . Death from any cause will be considered an event.
Measured: first: 18 months after inclusion of first patient, afterwards annually up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2013 (estimated)
- Study startApr 2013
- Primary completion1 Jun 2030 (estimated)
- Study completion1 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Anna Kinderkrebsforschung
- Sponsor type
- University, hospital or other
- Collaborators
- ALL SCTped Forum, European Society for Blood and Marrow Transplantation, ALL-BFM Study Group, Assistance Publique - Hôpitaux de Paris, Dutch Childhood Oncology Group, Swiss Pediatric Oncology Group, Australian & New Zealand Children's Haematology/Oncology Group
- Responsible party
- Sponsor
- Investigators
- Christina Peters, Prof. MD PhD, Study chair, St. Anna Kinderspital, Vienna, AustriaPeter Bader, Prof. MD PhD, Study chair, Goethe UniversityFranco Locatelli, Prof. MD PhD, Study chair, Ospedale Pediatrico Bambino Gesù, Rome, ItalyAnita Lawitschka, Assoc. Prof. MD, Study chair, St. Anna Kinderspital, Vienna, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949129
- Sponsor's protocol ID
- ALL SCTped FORUM 2012
- Status last verified
- Sep 2026
- First submitted
- 9 Sep 2013
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ben Hassine K, Gloor Y, Dupanloup I, Uppugunduri CRS, Mlakar V, Gonzales F, Gungor T, Ifversen M, Shaw PJ, Buechner J, Truong TH, Bittencourt H, Teague L, Toporski J, Sedlacek P, Poetschger U, Krajinovic M, Kalwak K, Balduzzi A, Algeri M, Bader P, Peters C, Dalle JH, Ansari M. Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study. Blood Adv. 2026 May 26;10(10):3719-3730. doi: 10.1182/bloodadvances.2025019142.
PubMed 41779961Buechner J, Poetschger U, Bader P, Yesilipek A, Pichler H, Palma J, Staciuk R, Riha P, Krivan G, Ifversen M, Gungor T, Goussetis E, Kalwak K, Toporski J, Gabriel M, Renard M, Diaz-de-Heredia C, Matic T, Calkoen FG, Svec P, Meisel R, Balduzzi A, Locatelli F, Peters C, Dalle JH, Stein J. Outcomes of BCP-ALL with hypodiploidy or BCR::ABL1 fusion in children undergoing allogeneic HSCT: results from the FORUM study. Blood. 2026 Mar 19;147(12):1365-1379. doi: 10.1182/blood.2025030951.
PubMed 41259231Greco R, Ruggeri A, McLornan DP, Snowden JA, Alexander T, Angelucci E, Averbuch D, Bazarbachi A, Hazenberg MD, Kalwak K, Kenyon M, Mekelenkamp H, Neven B, Pedrazzoli P, Peric Z, Risitano AM, Sanchez-Ortega I, Ciceri F, Sureda A. Indications for haematopoietic cell transplantation and CAR-T for haematological diseases, solid tumours and immune disorders: 2025 EBMT practice recommendations. Bone Marrow Transplant. 2025 Nov;60(11):1499-1525. doi: 10.1038/s41409-025-02701-3. Epub 2025 Sep 9.
PubMed 40926035Balduzzi A, Glogova E, Peters C, Sedlacek P, Dalle JH, Locatelli F, Meisel R, Burkhardt B, Buechner J, Wachowiak J, Bierings M, Staciuk R, Graphakos S, Gungor T, Yesilipek A, Svec P, Palma J, Krivan G, Diaz-de-Heredia C, Limido F, Ansari M, Kalwak K, Bader P, Ifversen M. Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM trial. Haematologica. 2026 Jan 1;111(1):122-134. doi: 10.3324/haematol.2025.287456. Epub 2025 Aug 7.
PubMed 40820816Kalwak K, Moser LM, Potschger U, Bader P, Kleinschmidt K, Meisel R, Dalle JH, Yesilipek A, Balduzzi A, Krivan G, Goussetis E, Staciuk R, Sedlacek P, Pichler H, Svec P, Gabriel M, Gungor T, Bilic E, Buechner J, Renard M, Vettenranta K, Ifversen M, Diaz-de-Heredia C, Stein J, Toporski J, Bierings M, Peters C, Ansari M, Locatelli F. Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM. Blood Adv. 2025 Feb 25;9(4):741-751. doi: 10.1182/bloodadvances.2024014548.
PubMed 39602342Bader P, Potschger U, Dalle JH, Moser LM, Balduzzi A, Ansari M, Buechner J, Gungor T, Ifversen M, Krivan G, Pichler H, Renard M, Staciuk R, Sedlacek P, Stein J, Heusel JR, Truong T, Wachowiak J, Yesilipek A, Locatelli F, Peters C. Low rate of nonrelapse mortality in under-4-year-olds with ALL given chemotherapeutic conditioning for HSCT: a phase 3 FORUM study. Blood Adv. 2024 Jan 23;8(2):416-428. doi: 10.1182/bloodadvances.2023010591.
PubMed 37738088Gomez SM, Varela MA, Ruiz C, Sung L. Comparable Outcomes of Matched Sibling Donor and Matched Unrelated Donor Stem Cell Transplantation in Children With Acute Leukemia in Argentina. J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e1020-e1024. doi: 10.1097/MPH.0000000000002174.
PubMed 33974585Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Gungor T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M; IBFM Study Group;; von Stackelberg A; IntReALL Study Group; Balduzzi A; I-BFM SCT Study Group; Corbacioglu S; EBMT Paediatric Diseases Working Party; Bader P. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. doi: 10.1200/JCO.20.02529. Epub 2020 Dec 17.
PubMed 33332189Tasian SK, Peters C. Targeted therapy or transplantation for paediatric ABL-class Ph-like acute lymphocytic leukaemia? Lancet Haematol. 2020 Dec;7(12):e858-e859. doi: 10.1016/S2352-3026(20)30369-0. No abstract available.
PubMed 33242441Choong E, Uppugunduri CRS, Marino D, Kuntzinger M, Doffey-Lazeyras F, Lo Piccolo R, Chalandon Y, Peters C, Daali Y, Ansari M. Therapeutic Drug Monitoring of Busulfan for the Management of Pediatric Patients: Cross-Validation of Methods and Long-Term Performance. Ther Drug Monit. 2018 Feb;40(1):84-92. doi: 10.1097/FTD.0000000000000468.
PubMed 29189665