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

Lymphoblastic Leukemia, Acute, Childhood; Clinical Trial

— ALL-SCT-BFMi  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01423500
• Other study ID #: EudraCT 2005-005106-23
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 23, 2011
• Last updated: June 25, 2015
• Start date: January 2007
• Est. completion date: September 2016

Study information

• Verified date: June 2015
• Source: St. Anna Kinderkrebsforschung
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Israel: The Israel National Institute for Health Policy Research and Health Services ResearchNetherlands: Medical Ethics Review Committee (METC)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug ControlSweden: Medical Products AgencyTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 405
• Est. completion date: September 2016
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 18 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Lymphoid
• Lymphoblastic Leukemia, Acute, Childhood;
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• VP16
patients with MSD receive as conditioning VP16 60mg/kg/d on day -3

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

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

Radiation:
• TBI
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)

Drug:
• 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
• 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

Radiation:
• TBI
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions

Locations

Country	Name	City	State
Austria	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
Czech Republic	Department of Paediatric Haematology and Oncology HSCT-Unit	Prague
Denmark	Pediatric Clinic II, Rigshospitalet	Copenhagen
France	Pediatric Immuno-Hematology Unit Robert Debré Hospital	Paris
Israel	Rambam Medical Center	Haifa
Israel	Schneider Children`s Medical Center of Israel	Petach-Tikva
Italy	Clinica Pediatrica dell`Universita di Milano Bicocca, Hospitale San Gerardo	Monza
Netherlands	Leiden University Hospital	Leiden
Netherlands	Radboud University - Nijmegen Medical Centre	Nijmegen
Netherlands	Department of Paediatric Haematology and Oncology, Wilhelmina Children's Hospital	Utrecht
Poland	University Hospital, Collegium Medicum UMK, Pediatric Hematology and Oncology	Bydgoszcz
Poland	Department of Transplantation, University Children's Hospital	Cracow
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
Slovakia	Department of Pediatric Bone Marrow Transplantation Unit, University Childrens´ Hospital	Bratislava
Sweden	Department of Pediatric Oncology, Lund University Hospital	Lund
Turkey	Department of Pediatrics, Gülhane Military Medical Academy	Ankara
Turkey	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	Department of Pediatric Hematology, Oncology and BMT, Istanbul School of Medicine	Istanbul
Turkey	Pediatric BMT Centre, Ege University	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
St. Anna Kinderkrebsforschung

Countries where clinical trial is conducted

Austria,  Czech Republic,  Denmark,  France,  Israel,  Italy,  Netherlands,  Poland,  Slovakia,  Sweden,  Turkey, 

References & Publications (3)

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, Klin — View Citation

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 wit — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival	Event-free and overall survival after allogeneic HSCT	10 years	Yes
Secondary	number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD)	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	10 years	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT	evaluation of organ dysfunctions according to WHO Toxicity score	10 years	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT	evaluation of growth retardation and endocrine dysfunction	10 years	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT	Evaluation of incidence of aseptic bone necrosis.	10 years	No
Secondary	occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT	Evaluation of incidence of secondary cancer after total body irradiation and/or chemotherapy	10 years	No

External Links

•   website St. Anna Children's Hospital