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

NCT ID: NCT01423500

Last Updated: 2015-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 405 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2016-09-30

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).

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 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 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

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 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

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 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

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 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

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; VP16: Etoposid; ATG: Antithymoglobuline; TBI: 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

St. Anna Kinderkrebsforschung

OTHER

Sponsor Role: lead

Responsible Party

Prof. Christina Peters

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christina Peters Peters, Prof MD PHD

Role: STUDY_CHAIR

St. Anna Kinderkrebsforschung

Petr Sedlacek, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Department of Paediatric Haematology and Oncology. HSCT Unit Prague

Marianne Ifversen, MD

Role: PRINCIPAL_INVESTIGATOR

Paediatric Clinic II, Rigshospitalet Copenhagen

Jean-Hugues Dalle, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

HSCT Unit Robert Debré Hospital Paris

Jerry Stein, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Schneider Children's Medical Center, Israel

Adriana Balduzzi, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale San Gerardo Monza

Marc Bierings, MD

Role: PRINCIPAL_INVESTIGATOR

Wilhelmina Children's Hospital Utrecht

Jacek Wachowiak, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

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

Sabina Sufliarska, MD

Role: PRINCIPAL_INVESTIGATOR

HSCT Unit, University Children's Hospital Bratislava

Jacek Toporski, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Paediatric Oncology Lund

Sema Anak, Prof MD

Role: PRINCIPAL_INVESTIGATOR

Paediatric HSCT Unit, Istanbul School of Medicine

Akif Yesilipek, MD Prof

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Graz, , Austria

Universitätsklinik für Kinder- und Jugendheilkunde

Innsbruck, , Austria

St. Anna Children's Hospital

Vienna, , Austria

Department of Paediatric Haematology and Oncology HSCT-Unit

Prague, , Czechia

Pediatric Clinic II, Rigshospitalet

Copenhagen, , Denmark

Pediatric Immuno-Hematology Unit Robert Debré Hospital

Paris, , France

Rambam Medical Center

Haifa, , Israel

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

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

Monza, , Italy

Leiden University Hospital

Leiden, , Netherlands

Radboud University - Nijmegen Medical Centre

Nijmegen, , Netherlands

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

Utrecht, , Netherlands

University Hospital, Collegium Medicum UMK, Pediatric Hematology and Oncology

Bydgoszcz, , Poland

Department of Transplantation, University Children's Hospital

Krakow, , Poland

Children's University Hospital - Hematology - Oncology

Lublin, , Poland

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

Poznan, , Poland

Wroclaw Medical University, Dept. of Children Hematology and Oncology

Wroclaw, , Poland

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

Bratislava, , Slovakia

Department of Pediatric Oncology, Lund University Hospital

Lund, , Sweden

Department of Pediatrics, Gülhane Military Medical Academy

Ankara, , Turkey (Türkiye)

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

Ankara, , Turkey (Türkiye)

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

Antalya, , Turkey (Türkiye)

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

Istanbul, , Turkey (Türkiye)

Pediatric BMT Centre, Ege University

Izmir, , Turkey (Türkiye)

Countries

Austria; Czechia; Denmark; France; Israel; Italy; Netherlands; Poland; Slovakia; Sweden; Turkey (Türkiye)

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)

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.

Reference Type: DERIVED

PMID: 31319153 (View on PubMed)

Other Identifiers

EudraCT 2005-005106-23

Identifier Type: -

Identifier Source: org_study_id