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

NCT01423747 | Unknown Phase 3 DMC

• 1 other identifier: ALL-SZT- BFM 2003
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 24

Brief Summary

With this protocol the ALL-SZT BFM international study group wants to evaluate whether hematopoietic stem cell transplantation (HSCT) from matched family or unrelated matched donors (MD) is equivalent to the HSCT from matched sibling donors (MSD). to evaluate the efficacy of haematopoietic stem cell transplantation (HSCT) from mismatched family or unrelated mismatched donors (MMD) as compared to HSCT from matched sibling donor (MSD) and matched donor (MD). to determine whether therapy has been carried out according to the main haematopoietic stem cell transplantation (HSCT) protocol recommendations. The standardisation of the treatment options during haematopoietic stem cell transplantation (HSCT) from different donor types aims at the achievement of an optimal comparison of survival after HSCT with survival after chemotherapy only. to prospectively evaluate and compare the incidence of acute and chronic graft- versus-host-disease (GvHD) after haematopoietic stem cell transplantation (HSCT) from matched sibling donor (MSD), from matched donor (MD) and from mismatched donor (MMD).

Conditions

Lymphoblastic Leukemia, Acute, Childhood;

Keywords

ALL; HSCT; children; adolescents

Outcome Measures

Primary Outcomes (1)

• Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)

  14 years

Secondary Outcomes (5)

• occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)

  14 years

• occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)

  14 years

• occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)

  14

• occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)

  14 years

• occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)

  14 years

Study Arms (3)

MSD - matched sibling donor

OTHER

patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)

Drug: VP16; Radiation: TBI

MD - matched donor

OTHER

patients with a HLA (Human Leukocyte Antigen) matched unrelated Donor (9/10 oder 10/10) receive total body irradiation (TBI) (12Gy in 6 fractions), VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1

Drug: VP16, ATG; Radiation: TBI

MMD - mismatched Donor

OTHER

Patients with a mismatched donor receive stem cells either from cord blood, a haploidentical donor (parent) or from a non-related donor with a match less or equal 8/10

Drug: Fludarabine, OKT3, Treosulfan, Thiotepa; Drug: VP16, ATG; Radiation: TBI

Interventions

VP16 DRUG

patients with MSD receive as conditioning VP16 60mg/kg/d on day -3

Also known as: Etoposid

MSD - matched sibling donor

TBI RADIATION

patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning

Also known as: total body irradiation

MSD - matched sibling donor

VP16, ATG DRUG

patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1

Also known as: Etoposid, Antithymoglobuline

MD - matched donor

Fludarabine, OKT3, Treosulfan, Thiotepa DRUG

patients with a MMD (haploidentical or cord blood) receive Fludarabine 30mg/m²/d on day -9 to -5, ATG 20mg/kd/d on day -3 to day -1, Treosulfan 14g/m²/d on day -7 to -5 and Thiotepa 2x5mg/kg/d on day -4

Also known as: ATG:Antithymoglobuline

MMD - mismatched Donor

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• age at time of initial diagnosis or relapse diagnosis, respectively under or equal 18 years
• indication for allogeneic hematopoietic stem cell transplantation (HSCT)
• complete remission before hematopoietic stem cell transplantation (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 hematopoietic stem cell transplantation (HSCT)
• hematopoietic stem cell transplantation (HSCT) is performed in a study participating centre.

You may not qualify if:

• age at time of initial diagnosis or relapse diagnosis, respectively above 18 years
• no indication for allogeneic HSCT
• no complete remission before SCT
• no written consent of the parents (legal guardian) and, if necessary, the minor patient via Informed Consent Form
• pregnancy
• secondary malignancy
• previous HSCT
• HSCT is not performed in a study participating centre.

Sponsors & Collaborators

• St. Anna Kinderkrebsforschung: lead
• International BFM Study Group: collaborator

Study Sites (24)

Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie

Graz, 8036, Austria

Location

Universitätsklinik für Kinder- und Jugendheilkunde

Innsbruck, 6020, Austria

Location

St. Anna Kinderspital

Vienna, 1090, Austria

Location

Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT

Berlin, 13353, Germany

Location

Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie

Düsseldorf, 40001, Germany

Location

Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg

Erlangen, 91054, Germany

Location

Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie

Essen, 45122, Germany

Location

Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie

Freiburg im Breisgau, 79106, Germany

Location

Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie

Giessen, 35385, Germany

Location

Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin

Halle, 06097, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie

Hamburg, 20246, Germany

Location

Med. Hochschule Hannover, Päd. Hämatologie und Onkologie

Hanover, 30625, Germany

Location

Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie

Heidelberg, 69120, Germany

Location

Klinik für Knochenmarktransplantation

Idar-Oberstein, 55743, Germany

Location

Klinik für Kinder- und Jugendmedizin

Jena, 07724, Germany

Location

Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie

Kiel, 24105, Germany

Location

Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie

München, 80337, Germany

Location

Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU

München, 80804, Germany

Location

Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie

Münster, 48149, Germany

Location

Univ.-Klinik für Kinderheilkunde und Jugendmedizin

Tübingen, 72076, Germany

Location

Universitätskinderklinik

Ulm, 89075, Germany

Location

Universitätsklinik, päd. Onkologie/Stammzelltransplantation

Würzburg, 97080, Germany

Location

Related Publications (6)

• Peters C, Schrauder A, Schrappe M, von Stackelberg A, Stary J, Yaniv I, Gadner H, Klingebiel T; BFM Study Group, the IBFM-Study Group and the Paediatric Disease Working Party of the EBMT. Allogeneic haematopoietic stem cell transplantation in children with acute lymphoblastic leukaemia: the BFM/IBFM/EBMT concepts. Bone Marrow Transplant. 2005 Mar;35 Suppl 1:S9-11. doi: 10.1038/sj.bmt.1704835.

  PMID: 15812540 RESULT

• Pulsipher MA, Peters C, Pui CH. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S137-48. doi: 10.1016/j.bbmt.2010.10.005.

  PMID: 21195303 RESULT

• Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: A prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. doi: 10.1200/JCO.2014.58.9747. Epub 2015 Mar 9.

  PMID: 25753432 RESULT

• Tasian 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.

  PMID: 33242441 DERIVED

• Preuner S, Peters C, Potschger U, Daxberger H, Fritsch G, Geyeregger R, Schrauder A, von Stackelberg A, Schrappe M, Bader P, Ebell W, Eckert C, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Lawitschka A, Mann G, Panzer-Grumayer R, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Lion T. Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia. Haematologica. 2016 Jun;101(6):741-6. doi: 10.3324/haematol.2015.135137. Epub 2016 Feb 11.

  PMID: 26869631 DERIVED

• Bader P, Kreyenberg H, von Stackelberg A, Eckert C, Salzmann-Manrique E, Meisel R, Poetschger U, Stachel D, Schrappe M, Alten J, Schrauder A, Schulz A, Lang P, Muller I, Albert MH, Willasch AM, Klingebiel TE, Peters C. Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1275-84. doi: 10.1200/JCO.2014.58.4631. Epub 2015 Jan 20.

  PMID: 25605857 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Etoposide; Whole-Body Irradiation; fludarabine; Muromonab-CD3; treosulfan; Thiotepa

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Radiotherapy; Therapeutics; Investigative Techniques; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Arend v. Stackelberg, MD, PhD

  ALL-REZ BFM Study Center Berlin Germany

  STUDY CHAIR

• Martin Schrappe, MD, Prof.

  ALL BFM study center Kiel, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 26, 2011
• Study Start: July 1, 2003
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2016
• Last Updated: June 26, 2015

Record last verified: 2015-06

Locations

DE (21); AU (3)