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

Sponsor

St. Anna Kinderkrebsforschung (Other)

Overall Status

Unknown status

CT.gov ID

NCT01423747

Collaborator

International BFM Study Group (Other)

400

Enrollment

Locations

Arms

158.1

Duration (Months)

16.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia, Acute, Childhood;	Drug: VP16 Radiation: TBI Drug: VP16, ATG Radiation: TBI Drug: Fludarabine, OKT3, Treosulfan, Thiotepa Drug: VP16, ATG Radiation: TBI	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2003

Actual Primary Completion Date :

Sep 1, 2011

Anticipated Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: MSD - matched sibling donor patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)	Drug: VP16 patients with MSD receive as conditioning VP16 60mg/kg/d on day -3 Other Names: Etoposid Radiation: TBI patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning Other Names: total body irradiation
Other: MD - matched donor patients with a HLA (Human Leukocyte Antigen) matched unrelated Donor (9/10 oder 10/10) receive total body irradiation (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 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 Other Names: Etoposid, Antithymoglobuline Radiation: TBI patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions) Other Names: total body irradiation
Other: MMD - mismatched Donor Patients with a mismatched donor 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 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 Other Names: ATG:Antithymoglobuline 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 Other Names: Etoposid, Antithymoglobuline Radiation: TBI patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions Other Names: total body irradiation

Arm

Intervention/Treatment

Other: MSD - matched sibling donor

patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)

Drug: VP16

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

Other Names:

Etoposid

Radiation: TBI

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

Other Names:

total body irradiation

Other: MD - matched donor

patients with a HLA (Human Leukocyte Antigen) matched unrelated Donor (9/10 oder 10/10) receive total body irradiation (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

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

Other Names:

Etoposid, Antithymoglobuline

Radiation: TBI

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

Other Names:

total body irradiation

Other: MMD - mismatched Donor

Patients with a mismatched donor 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

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

Other Names:

ATG:Antithymoglobuline

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

Other Names:

Etoposid, Antithymoglobuline

Radiation: TBI

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

Other Names:

total body irradiation

Outcome Measures

Primary Outcome Measures

Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT) [14 years]

Secondary Outcome Measures

occurrence of acute and chronic Graft-versus-Host-Disease (GvHD) [14 years]
Evaluation of the incidence and severity of acute Grade I-IV Graft-versus-Host-Disease (GvHD) and of limited or extensive chronic GvHD
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [14 years]
valuation of organ dysfunctions according to WHO Toxicity score
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [14]
evaluation of growth retardation and endocrine dysfunction
occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [14 years]
Evaluation of incidence of aseptic bone necrosis
occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT) [14 years]
Evaluation of incidence of secondary cancer after total body irradiation (TBI) and/or chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie	Graz	Austria	8036
2	Universitätsklinik für Kinder- und Jugendheilkunde	Innsbruck	Austria	6020
3	St. Anna Kinderspital	Vienna	Austria	1090
4	Charité Campus Virchow- Klinikum, Klinikum der Pädiatrie, Onkologie/Hämatologie/KMT	Berlin	Germany	13353
5	Klinik und Poliklinik für Kinderheilkunde, Hämatologie, Onkologie	Dresden	Germany	01307
6	Universitätsklinikum Düsseldorf, Klinik f. Kinderonkologie, Hämatologie u. Immunologie	Düsseldorf	Germany	40001
7	Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg	Erlangen	Germany	91054
8	Universitätsklinikum Essen, Zentrum für Kinderheilkunde, Abt. für Hämatologie/Onkologie	Essen	Germany	45122
9	Klinik für Kinderheilkunde III, Hämatologie und Onkologie, Johann Wolfgang Goethe Universität	Frankfurt am Main	Germany	60590
10	Universitätsklinikum Freiburg, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie	Freiburg	Germany	79106
11	Zentrum für Kinderheilkunde, Abt. Hämatologie und Onkologie	Giessen	Germany	35385
12	Klinkum der Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg, Uni. Klinik un Poliklinik für Kinder- und Jugendmedizin	Halle	Germany	06097
13	Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Abt. für Hämatologie und Onkologie	Hamburg	Germany	20246
14	Med. Hochschule Hannover, Päd. Hämatologie und Onkologie	Hannover	Germany	30625
15	Universitätskinderklinik, Päd. Hämatologie, Onkologie und Immunologie	Heidelberg	Germany	69120
16	Klinik für Knochenmarktransplantation	Idar-Oberstein	Germany	55743
17	Klinik für Kinder- und Jugendmedizin	Jena	Germany	07724
18	Universitätsklinikum Kiel, Klinik für Allgemeine Pädiatrie	Kiel	Germany	24105
19	Klinikum der Universität München, Dr. von Haunersches Kinderspital, Abt. für Hämatologie / Onkologie	München	Germany	80337
20	Städt. Krankenhaus München-Schwabing, Universitätskinderklinik der TU	München	Germany	80804
21	Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, päd. Hämatologie / Onkologie	Münster	Germany	48149
22	Univ.-Klinik für Kinderheilkunde und Jugendmedizin	Tübingen	Germany	72076
23	Universitätskinderklinik	Ulm	Germany	89075
24	Universitätsklinik, päd. Onkologie/Stammzelltransplantation	Würzburg	Germany	97080

Sponsors and Collaborators

St. Anna Kinderkrebsforschung
International BFM Study Group

Investigators

Study Chair: Arend v. Stackelberg, MD, PhD, ALL-REZ BFM Study Center Berlin Germany
Study Chair: Martin Schrappe, MD, Prof., ALL BFM study center Kiel, Germany