Clinical Trial

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

Dimensions: NCT01949129

Investigators

Stary, Jan (20)

Affiliations

Organisations

  1. (1) St.Anna Kinderspital, grid.477932.c
  2. (2) Goethe University Frankfurt, grid.7839.5
  3. (3) Bambino Gesù Children's Hospital, grid.414125.7
  4. (4) Garrahan Hospital, grid.414531.6
  5. (5) Graz University Hospital, grid.411580.9
  6. (6) University Hospital Innsbruck, grid.410706.4
  7. (7) St Anna Children's Hospital, grid.416346.2
  8. (8) Belarusian Research Center For Pediatric Oncology and Hematology, grid.428000.e
  9. (9) Queen Fabiola Children's University Hospital, grid.412209.c
  10. (10) Cliniques Universitaires Saint-Luc, grid.48769.34
  11. (11) Ghent University Hospital, grid.410566.0
  12. (12) Universitair Ziekenhuis Leuven, grid.410569.f
  13. (13) Centre Hospitalier Universitaire de Liège, grid.411374.4
  14. (14) Alberta Children's Hospital, grid.413571.5
  15. (15) Montreal Children's Hospital, grid.416084.f
  16. (16) Centre Hospitalier Universitaire Sainte-Justine, grid.411418.9
  17. (17) Hospital for Sick Children, grid.42327.30
  18. (18) British Columbia Children's Hospital, grid.414137.4
  19. (19) University of Manitoba, grid.21613.37
  20. (20) Charles University, grid.4491.8
  21. (21) Rigshospitalet, grid.475435.4, Capital Region
  22. (22) University of Helsinki, grid.7737.4
  23. (23) Centre Hospitalier Universitaire de Bordeaux, grid.42399.35
  24. (24) Centre Hospitalier Universitaire de Clermont-Ferrand, grid.411163.0
  25. (25) Hôpital Couple Enfant, grid.492672.c
  26. (26) Centre Hospitalier Régional et Universitaire de Lille, grid.410463.4
  27. (27) Hôpital de la Timone, grid.411266.6
  28. (28) Hôpital Arnaud De Villeneuve, grid.413745.0
  29. (29) Centre Hospitalier Universitaire de Nancy, grid.410527.5
  30. (30) Centre Hospitalier Universitaire de Nantes, grid.277151.7
  31. (31) Hôpital Robert Debré, grid.413235.2
  32. (32) Centre Hospitalier Universitaire de Rennes, grid.411154.4
  33. (33) Centre Hospitalier Universitaire de Rouen, grid.41724.34
  34. (34) Hôpitaux Universitaires de Strasbourg, grid.412220.7
  35. (35) University Hospital Aachen, grid.412301.5
  36. (36) Charité - University Medicine Berlin, grid.6363.0
  37. (37) Düsseldorf University Hospital, grid.14778.3d
  38. (38) University Hospital Erlangen, grid.411668.c
  39. (39) Essen University Hospital, grid.410718.b
  40. (40) Klinik für Kinder- und Jugendmedizin, grid.488569.e
  41. (41) University Medical Center Freiburg, grid.7708.8
  42. (42) University Hospital of Giessen and Marburg, grid.411067.5
  43. (43) University of Greifswald, grid.5603.0
  44. (44) University Hospital in Halle, grid.461820.9
  45. (45) University Medical Center Hamburg-Eppendorf, grid.13648.38
  46. (46) Hannover Medical School, grid.10423.34
  47. (47) University Hospital Heidelberg, grid.5253.1
  48. (48) Jena University Hospital, grid.275559.9
  49. (49) University Hospital Schleswig-Holstein, grid.412468.d
  50. (50) Klinikum der Universität München, grid.411095.8
  51. (51) Technical University of Munich, grid.6936.a
  52. (52) University Hospital Münster, grid.16149.3b
  53. (53) University Hospital Regensburg, grid.411941.8
  54. (54) University Children's Hospital Tübingen, grid.488549.c
  55. (55) University Hospital Ulm, grid.410712.1
  56. (56) Universitäts-Kinderklinik Würzburg, grid.488568.f
  57. (57) Rambam Health Care Campus, grid.413731.3
  58. (58) Schneider Children's Medical Center, grid.414231.1
  59. (59) Tel Aviv Sourasky Medical Center, grid.413449.f
  60. (60) Policlinico S.Orsola-Malpighi, grid.412311.4
  61. (61) Azienda Ospedaliera San Gerardo, grid.415025.7
  62. (62) Azienda Ospedaliera di Padova, grid.411474.3
  63. (63) Policlinico San Matteo Fondazione, grid.419425.f
  64. (64) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  65. (65) Ospedale Regina Margherita, grid.415778.8
  66. (66) University of Malaya, grid.10347.31
  67. (67) Leiden University Medical Center, grid.10419.3d
  68. (68) Princess Máxima Center, grid.487647.e
  69. (69) Starship Children's Health, grid.414054.0
  70. (70) Oslo University Hospital, grid.55325.34
  71. (71) University Children’s Hospital, grid.415112.2
  72. (72) Poznan University of Medical Sciences, grid.22254.33
  73. (73) Wrocław Medical University, grid.4495.c
  74. (74) Detská Fakultná Nemocnica s Poliklinikou, grid.470095.f
  75. (75) Ljubljana University Medical Centre, grid.29524.38
  76. (76) Hospital de Sant Pau, grid.413396.a
  77. (77) Vall d'Hebron Hospital Universitari, grid.411083.f
  78. (78) Hospital Universitario Virgen de la Arrixaca, grid.411372.2
  79. (79) Hospital Regional Universitario de Málaga, grid.411457.2
  80. (80) Central University Hospital of Asturias, grid.411052.3
  81. (81) Drottning Silvias barn- och ungdomssjukhus, grid.415579.b
  82. (82) Skåne University Hospital, grid.411843.b
  83. (83) Karolinska University Hospital, grid.24381.3c
  84. (84) Akademiska Barnsjukhuset, grid.488608.a
  85. (85) University Children’s Hospital Basel, grid.412347.7
  86. (86) University Hospital of Geneva, grid.150338.c
  87. (87) University Children's Hospital Zurich, grid.412341.1
  88. (88) Ankara University, grid.7256.6
  89. (89) Gazi University, grid.25769.3f
  90. (90) Akdeniz University, grid.29906.34
  91. (91) Bahçeşehir University, grid.10359.3e
  92. (92) Acıbadem University Atakent Hospital, grid.488402.2
  93. (93) Dokuz Eylül University, grid.21200.31
  94. (94) Ege University, grid.8302.9
  95. (95) Erciyes University, grid.411739.9

Sponsors/collaborators

Abstract

The ALL SCTped 2012 FORUM is a multinational, multi-centre, controlled, prospective phase III study for the therapy and therapy optimisation for children and adolescents with ALL in complete morphological remission (CR, less than 5% bone marrow blasts, no blasts in cerebrospinal fluid, no other extramedullary leukemia), who have an indication for HSCT with a myeloablative conditioning regimen. The stratification of patients in first and following remissions according to the individual transplantation modalities rests upon an indication for allogeneic HSCT and the availability of a suitable donor within the individual transplantation groups. Detailed Description Acute and late side effects of TBI in combination with other chemotherapeutic are manifold to the growing organism and include severe organ dysfunction/failure due to toxicity. Although transplant associated mortality was reduced after HSCT in the last decade due to better HLA matching, infection prevention and control, the burden of late complications is still a matter of concern. Growth retardation, hormonal dysfunction, sterility and the risk of secondary cancer are the late consequences of TBI in children. However, so far no prospective study has demonstrated similar outcomes in paediatric ALL using chemo-conditioning regimen before HSCT. The reason for that is manifold: only a minority of children with ALL qualifies for allogeneic HSCT as most patients are cured with sole modern chemotherapy approaches. Those with dismal prognosis are treated in HSCT centres offering a care to patients with different diseases. Therefore it is nearly impossible to answer the complex outcome questions in single centres or even in single countries. International cooperation is essential to allow prospective investigation within comparable patient cohorts. This study aimed to explore the efficacy and efficiency of two different chemo-conditioning regimens (Flu/Thio with Treo or ivBu) in comparison to the standard conditioning regimen (TBI/VP16). All patients with an indication for HSCT, age > 4 years and a matched donor (MD) or matched sibling donor (MSD) underwent a randomisation between these two conditioning regimens. The decision if the irradiation free conditioning is Flu/Thio/Treo or Flu/Thio/ivBu was stratified by country. Patients with age < 4 years received the irradiation free conditioning. Patients with a mismatched donor were stratified according to the donor's stem cell source (cordblood, haploidentical tx or bone marrow/peripheral blood stem cells). After an interim analysis of the randomized FORUM-trial in December 2018, which showed superior OS for TBI/Etoposide with equal outcomes for Bu or Treo-containing regimen, the randomization was suspended. The reason was less relapse incidence whereas 1-year TRM was comparable in all 3 arms. The randomization was closed in March 2019 based on the results of additional analyses confirming the superiority of TBI/VP16 over chemo-conditioning. Consequently, the TBI conditioning has remained a standard for the patients older than 4 years with a MSD/MD. Use of a conditioning other than TBI/VP16 in this age group is made at the center level based on the assessment of each individual patient.

Methods

Condition: Acute Lymphoblastic Leukaemia

Intervention: 30 mg/m² BS, 5 days

Recruitment information

Gender: All

Trial period

2013-2026

Phase

Phase 3

Research Categories

Main Subject Area

Fields of Research

External sources

Access at Registry