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

Sponsor

St. Anna Kinderkrebsforschung (Other)

Overall Status

Unknown status

CT.gov ID

NCT01423500

Collaborator

(none)

405

Enrollment

Locations

Arms

116

Duration (Months)

16.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

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 :

405 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 :

Jan 1, 2007

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 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 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	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 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	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 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: VP16: Etoposid ATG: Antithymoglobuline Radiation: TBI patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions Other Names: TBI: total body irradiation

Arm

Intervention/Treatment

Other: 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)

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 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

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 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

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

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:

VP16: Etoposid

ATG: Antithymoglobuline

Radiation: TBI

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

Other Names:

TBI: total body irradiation

Outcome Measures

Primary Outcome Measures

Event free survival [10 years]
Event-free and overall survival after allogeneic HSCT

Secondary Outcome Measures

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 HSCT [10 years]
evaluation of organ dysfunctions according to WHO Toxicity score
occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT [10 years]
evaluation of growth retardation and endocrine dysfunction
occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT [10 years]
Evaluation of incidence of aseptic bone necrosis.
occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT [10 years]
Evaluation of incidence of secondary cancer after total body irradiation 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 Children's Hospital	Vienna	Austria	A-1090
4	Department of Paediatric Haematology and Oncology HSCT-Unit	Prague	Czech Republic	15006
5	Pediatric Clinic II, Rigshospitalet	Copenhagen	Denmark	4074
6	Pediatric Immuno-Hematology Unit Robert Debré Hospital	Paris	France	75935
7	Rambam Medical Center	Haifa	Israel	31096
8	Schneider Children's Medical Center of Israel	Petach-Tikva	Israel	49202
9	Clinica Pediatrica dell'Universita di Milano Bicocca, Hospitale San Gerardo	Monza	Italy	20052
10	Leiden University Hospital	Leiden	Netherlands	2300
11	Radboud University - Nijmegen Medical Centre	Nijmegen	Netherlands	6500
12	Department of Paediatric Haematology and Oncology, Wilhelmina Children's Hospital	Utrecht	Netherlands	3584
13	University Hospital, Collegium Medicum UMK, Pediatric Hematology and Oncology	Bydgoszcz	Poland	85-094
14	Department of Transplantation, University Children's Hospital	Cracow	Poland	30-663
15	Children's University Hospital - Hematology - Oncology	Lublin	Poland	20-093
16	Department of Pediadric Oncology, Hematology and Transplantology, University of Medical Sciences	Poznan	Poland	60-572
17	Wroclaw Medical University, Dept. of Children Hematology and Oncology	Wroclaw	Poland	50-345
18	Department of Pediatric Bone Marrow Transplantation Unit, University Childrens´ Hospital	Bratislava	Slovakia	833 40
19	Department of Pediatric Oncology, Lund University Hospital	Lund	Sweden	221-85
20	Department of Pediatrics, Gülhane Military Medical Academy	Ankara	Turkey	06018
21	Dept. of Paediatrics - BMT Unit, School of Medicine, University of Ankara	Ankara	Turkey	06100
22	Department of Pediatric Hematology-Oncology and Pediatric Stem Cell Transplantation, Akdeniz University School of Medicine	Antalya	Turkey	07070
23	Department of Pediatric Hematology, Oncology and BMT, Istanbul School of Medicine	Istanbul	Turkey	343990
24	Pediatric BMT Centre, Ege University	Izmir	Turkey	35100

Sponsors and Collaborators

St. Anna Kinderkrebsforschung

Investigators

Study Chair: Christina Peters Peters, Prof MD PHD, St. Anna Kinderkrebsforschung
Principal Investigator: Petr Sedlacek, Prof. MD, Department of Paediatric Haematology and Oncology. HSCT Unit Prague
Principal Investigator: Marianne Ifversen, MD, Paediatric Clinic II, Rigshospitalet Copenhagen
Principal Investigator: Jean-Hugues Dalle, Prof. MD, HSCT Unit Robert Debré Hospital Paris
Principal Investigator: Jerry Stein, Prof. MD, Schneider Children's Medical Center, Israel
Principal Investigator: Adriana Balduzzi, MD, Ospedale San Gerardo Monza
Principal Investigator: Marc Bierings, MD, Wilhelmina Children's Hospital Utrecht
Principal Investigator: Jacek Wachowiak, MD, Prof., Department of Paediatric Oncology, Haematology and Transplantology, University of Medical Sciences Poznan
Principal Investigator: Sabina Sufliarska, MD, HSCT Unit, University Children's Hospital Bratislava
Principal Investigator: Jacek Toporski, MD, Department of Paediatric Oncology Lund
Principal Investigator: Sema Anak, Prof MD, Paediatric HSCT Unit, Istanbul School of Medicine
Principal Investigator: Akif Yesilipek, MD Prof, Dep. of Paediatric Haematology-Oncology and HSCT, Akdeniz University School of Medicine