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

NCT ID: NCT01423747

Last Updated: 2015-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2016-09-30

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).

Detailed Description

Patients with high risk or relapsed acute lymphoblastic leukaemia (ALL) have a worse prognosis compared to all other patients with ALL. For these patients additional therapy approaches are required after they have achieved remission with multimodal chemotherapy. Allogeneic haematopoetic stem cell transplantation shows promising results mainly due to an immunological antileukaemic control by the graft-versus-leukaemia effect, but treatment related mortality and morbidity remains a serious problem.

Conditions

Lymphoblastic Leukemia, Acute, Childhood;

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSD - matched sibling donor

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

Group Type: OTHER

VP16

Intervention Type: DRUG

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

TBI

Intervention Type: RADIATION

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

MD - matched donor

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

Group Type: OTHER

VP16, ATG

Intervention Type: 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

TBI

Intervention Type: RADIATION

patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)

MMD - mismatched Donor

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

Group Type: OTHER

Fludarabine, OKT3, Treosulfan, Thiotepa

Intervention Type: 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

VP16, ATG

Intervention Type: DRUG

patients with MMD-transplantation (8/10)receive VP16 60mg/kg/d on day -4, ATG from day -3 to day-1 20mg/kg/d

TBI

Intervention Type: RADIATION

patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions

Interventions

VP16

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

Intervention Type: DRUG

TBI

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

Intervention Type: RADIATION

VP16, ATG

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

Intervention Type: DRUG

TBI

patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)

Intervention Type: RADIATION

Fludarabine, OKT3, Treosulfan, Thiotepa

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

Intervention Type: DRUG

VP16, ATG

patients with MMD-transplantation (8/10)receive VP16 60mg/kg/d on day -4, ATG from day -3 to day-1 20mg/kg/d

Intervention Type: DRUG

TBI

patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions

Intervention Type: RADIATION

Other Intervention Names

Etoposid; total body irradiation; Etoposid, Antithymoglobuline; total body irradiation; ATG:Antithymoglobuline; Etoposid, Antithymoglobuline; total body irradiation

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International BFM Study Group

NETWORK

Sponsor Role: collaborator

St. Anna Kinderkrebsforschung

OTHER

Sponsor Role: lead

Responsible Party

Prof. Christina Peters

MD, PHD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arend v. Stackelberg, MD, PhD

Role: STUDY_CHAIR

ALL-REZ BFM Study Center Berlin Germany

Martin Schrappe, MD, Prof.

Role: STUDY_CHAIR

ALL BFM study center Kiel, Germany

Locations

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

Graz, , Austria

Universitätsklinik für Kinder- und Jugendheilkunde

Innsbruck, , Austria

St. Anna Kinderspital

Vienna, , Austria

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

Berlin, , Germany

Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie

Dresden, , Germany

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

Düsseldorf, , Germany

Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg

Erlangen, , Germany

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

Essen, , Germany

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

Frankfurt am Main, , Germany

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

Freiburg im Breisgau, , Germany

Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie

Giessen, , Germany

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

Halle, , Germany

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

Hamburg, , Germany

Med. Hochschule Hannover, Päd. Hämatologie und Onkologie

Hanover, , Germany

Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie

Heidelberg, , Germany

Klinik für Knochenmarktransplantation

Idar-Oberstein, , Germany

Klinik für Kinder- und Jugendmedizin

Jena, , Germany

Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie

Kiel, , Germany

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

München, , Germany

Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU

München, , Germany

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

Münster, , Germany

Univ.-Klinik für Kinderheilkunde und Jugendmedizin

Tübingen, , Germany

Universitätskinderklinik

Ulm, , Germany

Universitätsklinik, päd. Onkologie/Stammzelltransplantation

Würzburg, , Germany

Countries

Austria; Germany

References

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.

Reference Type: RESULT

PMID: 15812540 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21195303 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25753432 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33242441 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26869631 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25605857 (View on PubMed)

Other Identifiers

ALL-SZT- BFM 2003

Identifier Type: -

Identifier Source: org_study_id