ALL-SCT BFM International- HSCT in Children and Adolescents With ALL

NCT01423500 | Unknown Phase 3 DMC

• 1 other identifier: EudraCT 2005-005106-23
• Study Type: interventional
• Target: 405
• Locations: 11 countries
• Sites: 24

Brief Summary

With this protocol the ALL-SCT BFM international study group wants

• to evaluate whether hematopoietic stem cell transplantation (HSCT) from matched family or unrelated donors (MD) is equivalent to the HSCT from matched sibling donors (MSD).
• to evaluate the efficacy of hematopoietic stem cell transplantation (HSCT)from mismatched family or unrelated donors (MMD) as compared to HSCT from matched sibling donors or matched donors.
• to determine whether therapy has been carried out according to the main HSCT protocol recommendations. The standardisation of the treatment options during 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 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 survival

  Event-free and overall survival after allogeneic HSCT

  10 years

Secondary Outcomes (5)

• number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD)

  10 years

• occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT

  10 years

• occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT

  10 years

• occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT

  10 years

• occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT

  10 years

Study Arms (3)

MSD - Matched Sibling Donor

OTHER

patients with a MSD receive a conditioning of 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 matched unrelated Donor (9/10 oder 10/10) receive 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 MMD 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

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

TBI RADIATION

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

Also known as: Total body irradiation

MSD - Matched Sibling 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 fresenius 20mg/kg/d on day -3,-2,-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

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 Children's Hospital

Vienna, A-1090, Austria

Location

Department of Paediatric Haematology and Oncology HSCT-Unit

Prague, 15006, Czechia

Location

Pediatric Clinic II, Rigshospitalet

Copenhagen, 4074, Denmark

Location

Pediatric Immuno-Hematology Unit Robert Debré Hospital

Paris, 75935, France

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 49202, Israel

Location

Clinica Pediatrica dell'Universita di Milano Bicocca, Hospitale San Gerardo

Monza, 20052, Italy

Location

Leiden University Hospital

Leiden, 2300, Netherlands

Location

Radboud University - Nijmegen Medical Centre

Nijmegen, 6500, Netherlands

Location

Department of Paediatric Haematology and Oncology, Wilhelmina Children's Hospital

Utrecht, 3584, Netherlands

Location

University Hospital, Collegium Medicum UMK, Pediatric Hematology and Oncology

Bydgoszcz, 85-094, Poland

Location

Department of Transplantation, University Children's Hospital

Krakow, 30-663, Poland

Location

Children's University Hospital - Hematology - Oncology

Lublin, 20-093, Poland

Location

Department of Pediadric Oncology, Hematology and Transplantology, University of Medical Sciences

Poznan, 60-572, Poland

Location

Wroclaw Medical University, Dept. of Children Hematology and Oncology

Wroclaw, 50-345, Poland

Location

Department of Pediatric Bone Marrow Transplantation Unit, University Childrens´ Hospital

Bratislava, 833 40, Slovakia

Location

Department of Pediatric Oncology, Lund University Hospital

Lund, 221-85, Sweden

Location

Department of Pediatrics, Gülhane Military Medical Academy

Ankara, 06018, Turkey (Türkiye)

Location

Dept. of Paediatrics - BMT Unit, School of Medicine, University of Ankara

Ankara, 06100, Turkey (Türkiye)

Location

Department of Pediatric Hematology-Oncology and Pediatric Stem Cell Transplantation, Akdeniz University School of Medicine

Antalya, 07070, Turkey (Türkiye)

Location

Department of Pediatric Hematology, Oncology and BMT, Istanbul School of Medicine

Istanbul, 343990, Turkey (Türkiye)

Location

Pediatric BMT Centre, Ege University

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (5)

• 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

• Balduzzi A, Dalle JH, Wachowiak J, Yaniv I, Yesilipek A, Sedlacek P, Bierings M, Ifversen M, Sufliarska S, Kalwak K, Lankester A, Toporski J, Di Maio L, Glogova E, Poetschger U, Peters C. Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia from a Matched Donor versus an HLA-Identical Sibling: Is the Outcome Comparable? Results from the International BFM ALL SCT 2007 Study. Biol Blood Marrow Transplant. 2019 Nov;25(11):2197-2210. doi: 10.1016/j.bbmt.2019.07.011. Epub 2019 Jul 15.

  PMID: 31319153 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

• Christina Peters Peters, Prof MD PHD

  St. Anna Kinderkrebsforschung

  STUDY CHAIR

• Petr Sedlacek, Prof. MD

  Department of Paediatric Haematology and Oncology. HSCT Unit Prague

  PRINCIPAL INVESTIGATOR

• Marianne Ifversen, MD

  Paediatric Clinic II, Rigshospitalet Copenhagen

  PRINCIPAL INVESTIGATOR

• Jean-Hugues Dalle, Prof. MD

  HSCT Unit Robert Debré Hospital Paris

  PRINCIPAL INVESTIGATOR

• Jerry Stein, Prof. MD

  Schneider Children's Medical Center, Israel

  PRINCIPAL INVESTIGATOR

• Adriana Balduzzi, MD

  Ospedale San Gerardo Monza

  PRINCIPAL INVESTIGATOR

• Marc Bierings, MD

  Wilhelmina Children's Hospital Utrecht

  PRINCIPAL INVESTIGATOR

• Jacek Wachowiak, MD, Prof.

  Department of Paediatric Oncology, Haematology and Transplantology, University of Medical Sciences Poznan

  PRINCIPAL INVESTIGATOR

• Sabina Sufliarska, MD

  HSCT Unit, University Children's Hospital Bratislava

  PRINCIPAL INVESTIGATOR

• Jacek Toporski, MD

  Department of Paediatric Oncology Lund

  PRINCIPAL INVESTIGATOR

• Sema Anak, Prof MD

  Paediatric HSCT Unit, Istanbul School of Medicine

  PRINCIPAL INVESTIGATOR

• Akif Yesilipek, MD Prof

  Dep. of Paediatric Haematology-Oncology and HSCT, Akdeniz University School of Medicine

  PRINCIPAL INVESTIGATOR

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 23, 2011
• First Posted: August 26, 2011
• Study Start: January 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2016
• Last Updated: June 26, 2015

Record last verified: 2015-06

Locations

SL (1); TU (5); IT (1); DK (1); NL (3); AU (3); IL (2); FR (1); PL (5); CZ (1); SE (1)