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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
International BFM Study Group
Information provided by (Responsible Party):
Prof. Christina Peters, St. Anna Kinderspital, Austria
ClinicalTrials.gov Identifier:
NCT01423747
First received: August 25, 2011
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Lymphoblastic Leukemia, Acute, Childhood;
Drug: VP16
Radiation: TBI
Drug: VP16, ATG
Drug: Fludarabine, OKT3, Treosulfan, Thiotepa
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia

Resource links provided by NLM:


Further study details as provided by St. Anna Kinderkrebsforschung:

Primary Outcome Measures:
  • Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT) [ Time Frame: 14 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • occurrence of acute and chronic Graft-versus-Host-Disease (GvHD) [ Time Frame: 14 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 ] [ Designated as safety issue: No ]
    evaluation of growth retardation and endocrine dysfunction

  • occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [ Time Frame: 14 years ] [ Designated as safety issue: No ]
    Evaluation of incidence of aseptic bone necrosis

  • occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [ Time Frame: 14 years ] [ Designated as safety issue: No ]
    Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy


Estimated Enrollment: 400
Study Start Date: July 2003
Estimated Study Completion Date: September 2016
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Etoposid
Radiation: TBI
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
Other Name: total body irradiation
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
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 Name: Etoposid, Antithymoglobuline
Radiation: TBI
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
Other Name: total body irradiation
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
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 Name: ATG: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 Name: Etoposid, Antithymoglobuline
Radiation: TBI
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Other Name: total body irradiation

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.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423747

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

Additional Information:
Publications:
Responsible Party: Prof. Christina Peters, MD, PHD, St. Anna Kinderspital, Austria
ClinicalTrials.gov Identifier: NCT01423747     History of Changes
Other Study ID Numbers: ALL-SZT- BFM 2003
Study First Received: August 25, 2011
Last Updated: August 19, 2014
Health Authority: Austria: Federal Ministry for Health Family and Youth

Keywords provided by St. Anna Kinderkrebsforschung:
ALL
HSCT
children
adolescents

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Etoposide phosphate
Treosulfan
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 16, 2014