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

Lymphoblastic Leukemia, Acute, Childhood; Clinical Trial

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: NCT01423747
• Other study ID #: ALL-SZT- BFM 2003
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 25, 2011
• Last updated: June 25, 2015
• Start date: July 2003
• 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 Ministry for Health Family and Youth
• Study type: Interventional

Clinical Trial Summary

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).

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: 400
• 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
• 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 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
• 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 Kinderspital	Vienna
Germany	Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT	Berlin
Germany	Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie	Dresden
Germany	Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie	Düsseldorf
Germany	Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg	Erlangen
Germany	Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie	Essen
Germany	Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität	Frankfurt am Main
Germany	Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie	Freiburg
Germany	Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie	Giessen
Germany	Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie	Hamburg
Germany	Med. Hochschule Hannover, Päd. Hämatologie und Onkologie	Hannover
Germany	Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie	Heidelberg
Germany	Klinik für Knochenmarktransplantation	Idar-Oberstein
Germany	Klinik für Kinder- und Jugendmedizin	Jena
Germany	Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie	Kiel
Germany	Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie	München
Germany	Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU	München
Germany	Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie	Münster
Germany	Univ.-Klinik für Kinderheilkunde und Jugendmedizin	Tübingen
Germany	Universitätskinderklinik	Ulm
Germany	Universitätsklinik, päd. Onkologie/Stammzelltransplantation	Würzburg

Sponsors (2)

Lead Sponsor	Collaborator
St. Anna Kinderkrebsforschung	International BFM Study Group

Countries where clinical trial is conducted

Austria,  Germany, 

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 and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)		14 years	Yes
Secondary	occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)	Evaluation of the incidence and severity of acute Grade I-IV Graft-versus-Host-Disease (GvHD) and of limited or extensive chronic GvHD	14 years	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)	valuation of organ dysfunctions according to WHO Toxicity score	14 years	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)	evaluation of growth retardation and endocrine dysfunction	14	No
Secondary	occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)	Evaluation of incidence of aseptic bone necrosis	14 years	No
Secondary	occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)	Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy	14 years	No

External Links

•   Web Site St. Anna Children's Hospital