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

June 25, 2015 updated by: Prof. Christina Peters, St. Anna Kinderkrebsforschung

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • 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 Locations

  • Austria
      • Graz, Austria, 8036
        • Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie
      • Innsbruck, Austria, 6020
        • Universitätsklinik für Kinder- und Jugendheilkunde
      • Vienna, Austria, 1090
        • St. Anna Kinderspital
  • Germany
      • Berlin, Germany, 13353
        • Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT
      • Dresden, Germany, 01307
        • Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie
      • Düsseldorf, Germany, 40001
        • Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie
      • Erlangen, Germany, 91054
        • Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg
      • Essen, Germany, 45122
        • Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie
      • Frankfurt am Main, Germany, 60590
        • Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität
      • Freiburg, Germany, 79106
        • Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie
      • Giessen, Germany, 35385
        • Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie
      • Halle, Germany, 06097
        • Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie
      • Hannover, Germany, 30625
        • Med. Hochschule Hannover, Päd. Hämatologie und Onkologie
      • Heidelberg, Germany, 69120
        • Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie
      • Idar-Oberstein, Germany, 55743
        • Klinik für Knochenmarktransplantation
      • Jena, Germany, 07724
        • Klinik für Kinder- und Jugendmedizin
      • Kiel, Germany, 24105
        • Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie
      • München, Germany, 80337
        • Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie
      • München, Germany, 80804
        • Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU
      • Münster, Germany, 48149
        • Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie
      • Tübingen, Germany, 72076
        • Univ.-Klinik für Kinderheilkunde und Jugendmedizin
      • Ulm, Germany, 89075
        • Universitätskinderklinik
      • Würzburg, Germany, 97080
        • Universitätsklinik, päd. Onkologie/Stammzelltransplantation

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

3 months to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: 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)
Drug: VP16
patients with MSD receive as conditioning VP16 60mg/kg/d on day -3
Other Names:
  • Etoposid
Radiation: TBI
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
Other Names:
  • total body irradiation
Radiation: TBI
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
Other Names:
  • total body irradiation
Radiation: TBI
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Other Names:
  • total body irradiation
OTHER: 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
Radiation: TBI
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
Other Names:
  • total body irradiation
Radiation: TBI
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
Other Names:
  • total body irradiation
Radiation: TBI
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Other Names:
  • total body irradiation
Drug: 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
Other Names:
  • Etoposid, Antithymoglobuline
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
Other Names:
  • Etoposid, Antithymoglobuline
OTHER: 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
Radiation: TBI
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
Other Names:
  • total body irradiation
Radiation: TBI
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
Other Names:
  • total body irradiation
Radiation: TBI
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Other Names:
  • total body irradiation
Drug: 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
Other Names:
  • Etoposid, Antithymoglobuline
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
Other Names:
  • Etoposid, Antithymoglobuline
Drug: 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
Other Names:
  • ATG:Antithymoglobuline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)
Time Frame: 14 years
14 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)
Time Frame: 14 years
Evaluation of the incidence and severity of acute Grade I-IV Graft-versus-Host-Disease (GvHD) and of limited or extensive chronic GvHD
14 years
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Time Frame: 14 years
valuation of organ dysfunctions according to WHO Toxicity score
14 years
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Time Frame: 14
evaluation of growth retardation and endocrine dysfunction
14
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Time Frame: 14 years
Evaluation of incidence of aseptic bone necrosis
14 years
occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)
Time Frame: 14 years
Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy
14 years

Collaborators and Investigators

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

Sponsor

St. Anna Kinderkrebsforschung

Collaborators

International BFM Study Group

Investigators

  • Study Chair: Arend v. Stackelberg, MD, PhD, ALL-REZ BFM Study Center Berlin Germany
  • Study Chair: Martin Schrappe, MD, Prof., ALL BFM study center Kiel, Germany

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

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

July 1, 2003

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ANTICIPATED)

September 1, 2016

Study Registration Dates

First Submitted

August 25, 2011

First Submitted That Met QC Criteria

August 25, 2011

First Posted (ESTIMATE)

August 26, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

June 26, 2015

Last Update Submitted That Met QC Criteria

June 25, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALL-SZT- BFM 2003

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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