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

Primary Purpose

Lymphoblastic Leukemia, Acute, Childhood;

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VP16
TBI
VP16, ATG
TBI
Fludarabine, OKT3, Treosulfan, Thiotepa
VP16, ATG
TBI
Sponsored by
St. Anna Kinderkrebsforschung
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia, Acute, Childhood; focused on measuring ALL, HSCT, children, adolescents

Eligibility Criteria

3 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie
  • Universitätsklinik für Kinder- und Jugendheilkunde
  • St. Anna Kinderspital
  • Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT
  • Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie
  • Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie
  • Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg
  • Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie
  • Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität
  • Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie
  • Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie
  • Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin
  • Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie
  • Med. Hochschule Hannover, Päd. Hämatologie und Onkologie
  • Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie
  • Klinik für Knochenmarktransplantation
  • Klinik für Kinder- und Jugendmedizin
  • Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie
  • Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie
  • Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU
  • Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie
  • Univ.-Klinik für Kinderheilkunde und Jugendmedizin
  • Universitätskinderklinik
  • Universitätsklinik, päd. Onkologie/Stammzelltransplantation

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

MSD - matched sibling donor

MD - matched donor

MMD - mismatched Donor

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)
Evaluation of the incidence and severity of acute Grade I-IV Graft-versus-Host-Disease (GvHD) and of limited or extensive chronic GvHD
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
valuation of organ dysfunctions according to WHO Toxicity score
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
evaluation of growth retardation and endocrine dysfunction
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Evaluation of incidence of aseptic bone necrosis
occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy

Full Information

First Posted
August 25, 2011
Last Updated
June 25, 2015
Sponsor
St. Anna Kinderkrebsforschung
Collaborators
International BFM Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT01423747
Brief Title
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia
Official Title
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Unknown status
Study Start Date
July 2003 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Anna Kinderkrebsforschung
Collaborators
International BFM Study Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Acute, Childhood;
Keywords
ALL, HSCT, children, adolescents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MSD - matched sibling donor
Arm Type
Other
Arm Description
patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)
Arm Title
MD - matched donor
Arm Type
Other
Arm Description
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
Arm Title
MMD - mismatched Donor
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
VP16
Other Intervention Name(s)
Etoposid
Intervention Description
patients with MSD receive as conditioning VP16 60mg/kg/d on day -3
Intervention Type
Radiation
Intervention Name(s)
TBI
Other Intervention Name(s)
total body irradiation
Intervention Description
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
Intervention Type
Drug
Intervention Name(s)
VP16, ATG
Other Intervention Name(s)
Etoposid, Antithymoglobuline
Intervention Description
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
Radiation
Intervention Name(s)
TBI
Other Intervention Name(s)
total body irradiation
Intervention Description
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
Intervention Type
Drug
Intervention Name(s)
Fludarabine, OKT3, Treosulfan, Thiotepa
Other Intervention Name(s)
ATG:Antithymoglobuline
Intervention Description
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
Intervention Name(s)
VP16, ATG
Other Intervention Name(s)
Etoposid, Antithymoglobuline
Intervention Description
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
Radiation
Intervention Name(s)
TBI
Other Intervention Name(s)
total body irradiation
Intervention Description
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Primary Outcome Measure Information:
Title
Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)
Time Frame
14 years
Secondary Outcome Measure Information:
Title
occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)
Description
Evaluation of the incidence and severity of acute Grade I-IV Graft-versus-Host-Disease (GvHD) and of limited or extensive chronic GvHD
Time Frame
14 years
Title
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Description
valuation of organ dysfunctions according to WHO Toxicity score
Time Frame
14 years
Title
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Description
evaluation of growth retardation and endocrine dysfunction
Time Frame
14
Title
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Description
Evaluation of incidence of aseptic bone necrosis
Time Frame
14 years
Title
occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Description
Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy
Time Frame
14 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arend v. Stackelberg, MD, PhD
Organizational Affiliation
ALL-REZ BFM Study Center Berlin Germany
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Martin Schrappe, MD, Prof.
Organizational Affiliation
ALL BFM study center Kiel, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Universitätsklinik für Kinder- und Jugendheilkunde
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
St. Anna Kinderspital
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie
City
Düsseldorf
ZIP/Postal Code
40001
Country
Germany
Facility Name
Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie
City
Giessen
ZIP/Postal Code
35385
Country
Germany
Facility Name
Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin
City
Halle
ZIP/Postal Code
06097
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Med. Hochschule Hannover, Päd. Hämatologie und Onkologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Klinik für Knochenmarktransplantation
City
Idar-Oberstein
ZIP/Postal Code
55743
Country
Germany
Facility Name
Klinik für Kinder- und Jugendmedizin
City
Jena
ZIP/Postal Code
07724
Country
Germany
Facility Name
Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie
City
München
ZIP/Postal Code
80337
Country
Germany
Facility Name
Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU
City
München
ZIP/Postal Code
80804
Country
Germany
Facility Name
Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Univ.-Klinik für Kinderheilkunde und Jugendmedizin
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitätskinderklinik
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Facility Name
Universitätsklinik, päd. Onkologie/Stammzelltransplantation
City
Würzburg
ZIP/Postal Code
97080
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
15812540
Citation
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.
Results Reference
result
PubMed Identifier
21195303
Citation
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.
Results Reference
result
PubMed Identifier
25753432
Citation
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.
Results Reference
result
PubMed Identifier
33242441
Citation
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.
Results Reference
derived
PubMed Identifier
26869631
Citation
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.
Results Reference
derived
PubMed Identifier
25605857
Citation
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.
Results Reference
derived

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

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