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

Phase 3
Conditions
Lymphoblastic Leukemia, Acute, Childhood;
Interventions
Drug: Fludarabine, OKT3, Treosulfan, Thiotepa
Drug: VP16, ATG
Radiation: TBI
Registration Number
NCT01423500
Lead Sponsor
St. Anna Kinderkrebsforschung
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
405
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MMD - Mismatched DonorFludarabine, OKT3, Treosulfan, ThiotepaPatients 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
MMD - Mismatched DonorTBIPatients 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
MSD - Matched Sibling DonorTBIpatients with a MSD receive a conditioning of TBI (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)
MMD - Mismatched DonorVP16, ATGPatients 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
MSD - Matched Sibling DonorVP16patients with a MSD receive a conditioning of TBI (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)
MD - Matched DonorVP16, ATGpatients 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
MD - Matched DonorTBIpatients 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
Primary Outcome Measures
NameTimeMethod
Event free survival10 years

Event-free and overall survival after allogeneic HSCT

Secondary Outcome Measures
NameTimeMethod
number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD)10 years

evaluation of the incidence and severity of acute Grade I-IV graft versus Host disease and of limited or extensive chronic graft versus host disease

occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT10 years

Evaluation of incidence of aseptic bone necrosis.

occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT10 years

Evaluation of incidence of secondary cancer after total body irradiation and/or chemotherapy

Trial Locations

Locations (24)

Pediatric Immuno-Hematology Unit Robert Debré Hospital

🇫🇷

Paris, France

Leiden University Hospital

🇳🇱

Leiden, Netherlands

Department of Pediatric Oncology, Lund University Hospital

🇸🇪

Lund, Sweden

Pediatric Clinic II, Rigshospitalet

🇩🇰

Copenhagen, Denmark

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

🇮🇹

Monza, Italy

Department of Pediatrics, Gülhane Military Medical Academy

🇹🇷

Ankara, Turkey

Pediatric BMT Centre, Ege University

🇹🇷

Izmir, Turkey

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

🇦🇹

Graz, Austria

Children's University Hospital - Hematology - Oncology

🇵🇱

Lublin, Poland

Department of Paediatric Haematology and Oncology HSCT-Unit

🇨🇿

Prague, Czech Republic

Radboud University - Nijmegen Medical Centre

🇳🇱

Nijmegen, Netherlands

Schneider Children's Medical Center of Israel

🇮🇱

Petach-Tikva, Israel

Department of Transplantation, University Children's Hospital

🇵🇱

Cracow, Poland

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

🇸🇰

Bratislava, Slovakia

St. Anna Children's Hospital

🇦🇹

Vienna, Austria

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

🇳🇱

Utrecht, Netherlands

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

🇹🇷

Ankara, Turkey

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

🇹🇷

Antalya, Turkey

Universitätsklinik für Kinder- und Jugendheilkunde

🇦🇹

Innsbruck, Austria

Rambam Medical Center

🇮🇱

Haifa, Israel

University Hospital, Collegium Medicum UMK, Pediatric Hematology and Oncology

🇵🇱

Bydgoszcz, 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 Hematology, Oncology and BMT, Istanbul School of Medicine

🇹🇷

Istanbul, Turkey

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