Studying Conditioning Regimen In Pediatric Transplantation - AML , SCRIPT-AML
- Conditions
- Stem Cell TransplantationAcute Myeloid Leukemia (AML) in Remission
- Interventions
- Registration Number
- NCT05477589
- Lead Sponsor
- Vastra Gotaland Region
- Brief Summary
It is a randomized phase 3 study comparing two conditioning regimens in children with Acute Myeloid Leukemia, AML, undergoing allogenic stem cell transplantation. The primary aim is to investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival than a conditioning regimen combining three alkylating agents (BuCyMel)
- Detailed Description
The study is designed as an open-label randomized phase III, multicenter superiority trial comparing two conditioning regimens CloFluBu and BuCyMel in children with acute myeloid leukemia (AML) with per-protocol indications to allogeneic hematopoietic stem cell transplantation with a myeloablative conditioning.
This study is composed of two parts - an interventional part that includes randomization, and an observational part. The interventional part is a phase III randomized, open label, multicenter parallel group trial comparing two conditioning regimens used in pediatric HCT: a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm) and a combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm). The observational part will prospectively register outcome measures of transplantation in patients not fulfilling criteria for participation in the interventional part of the study (due to lack of complete remission, lack of matched sibling or unrelated donor, who were not recruited to a national upfront protocol or who decline participation in randomization) but consenting to registration of the data.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description BuCyMel busulfan, cyclophosphamide and melphalan, BuCyMel a combination of busulfan, cyclophosphamide and melphalan, conditioning regimen CloFluBu clofarabine, fludarabine and busulfan, CloFluBu a combination of clofarabine, fludarabine and busulfan conditioning regimen
- Primary Outcome Measures
Name Time Method 2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF) 2 years To investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival (GRFS) than a conditioning regimen combining three alkylating agents (BuCyMel)
- Secondary Outcome Measures
Name Time Method Neutrophil and platelet engraftment 28 days post transplantation time to engraftment after stem cells transplantation, in all patients
Primary graft failure +28 days post transplantation The incidence of graft failure defined as neutrophil recovery by day +28 post transplantation
Secondary graft failure 2 years The incidence of secondary graft failure
The association between pre-HCT MRD and relapse 2 years % of remaining leukemic cells in the last bone marrow sample taken before start of conditioning
Cumulative incidence of transplant-related mortality 2 years The incidence of transplant-related mortality at 2 years
Disease-free survival 2 years Disease-free survival at 2 years
Overall survival 2 years Overall survival at 2 years
Immunological recovery 2 years Immunological recovery of CD3+ and CD4+ cells in peripheral blood
Incidence of grade II-IV and III-IV acute GVHD +180 days post transplantation The incidence of acute GvHD
Incidence of chronic GVHD 2 years The incidence of cGVHD
Incidence of grade ≥ 3 toxicity Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease + 100 days post transplantation The rates of grade ≥ 3 Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease
Incidence of grade ≥ 3 toxicity Engraftment Syndrome (ES) 2 years The incidence of engraftment syndome
Incidence of grade ≥ 3 toxicity Transplant-associated thrombotic microangiopathy (TA-TMA) 2 years The incidence of TA-TMA
Incidence of grade ≥ 3 toxicity Hemorrhagic Cystitis (HC) 2 years The incidence of HC
Incidence of grade ≥ 3 infections 2 years The incidence of grade ≥ 3 infections of bacterial, viral and fungal origin
Health-Related Quality of Life, HRQoL. 2 years HRQoL will be measured at baseline and at certain intervals using the quality of life instrument EQ-5D-Y, (Youth)™which include 2 measurements, the descriptive scale ( i.g. the score 1 is no problems and 3 is a lot of problems) and the VAS scale( 1 is the worst health and 100 is the best health that day).
Transplant-associated hormonal and gonadal late effects 2 years the date of spontaneous puberty, date of spontaneous menarche for female patients and mean testicular volume for male patients, use of hormonal replacement therapy and use of fertility preservation
Nutritional status 2 years BMI in kg/m\^2 at baseline and post transplantation
Cumulative incidence of relapse 2 years The incidence of cumulative incidence of relapse during the first two years after transplantation
Trial Locations
- Locations (17)
L'Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc (CUSL)
🇧🇪Brussels, Belgium
Department of Pediatric Hematology, Oncology and SCT, Ghent University Hospital
🇧🇪Ghent, Belgium
University Hospital Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Régional de la Citadelle (CHR)/CHU Liège
🇧🇪Liège, Belgium
Paediatric Stem Cell Transplant and Immune Deficiency, Department of Pediatric and Adolescent Medicine, Section 4072, Rigshospitalet University Hospital of Copenhagen
🇩🇰Copenhagen, Denmark
Division of Hematology, Oncology, and Stem Cell Transplantation, The New Children's Hospital, Helsinki University Hospital
🇫🇮Helsinki, Finland
Department of Pediatrics and Adolescent Medicine, Hong King Children's Hospital
🇭🇰Hong Kong, Hong Kong
Schneider Children's Medical Center of Israel
🇮🇱Petach Tikva, Israel
Vilnius University Hospital Santaros Klinikos Center for Pediatric Oncology and Hematology
🇱🇹Vilnius, Lithuania
Princess Máxima Center for Pediatric Oncology
🇳🇱Utrecht, Netherlands
Department of Pediatric Hematology and Oncology, Oslo University HospitalOslo University Hospital
🇳🇴Oslo, Norway
Stemcelltransplant unit Hospital Niño Jesús
🇪🇸Madrid, Spain
Queen Silvia Children's Hospital, Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Barncancercentrum, avdelning 64, Skane University Hospital
🇸🇪Lund, Sweden
Pediatric Hematology immunology and stem cell transplantation Astrid Lindgren children's Hospital Huddinge K86-88
🇸🇪Stockholm, Sweden
Childrens department for Blood and tumor diseases Uppsala University Hospital
🇸🇪Uppsala, Sweden