Acute myeloid leukemia (AML) in children
Conditions
Sponsors
Västra Götalands Regionen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for randomization part of the study - Age =18 years at time of initial AML, age = 21 years at transplantation. -All women of childbearing potential who have to have a negative pregnancy test within 2 weeks prior to the start of treatment. - Signed informed consent. - Any relapsed AML after initial treatment according to a defined international AML protocol. (NOPHO-DBH AML 2012/new protocol), OR AML in first remission with transplant indications and treatment according to national AML protocol (NOPHO-DBH AML 2012 or new protocol). - In hematological remission, defined as o =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria for the randomization part of the study Patients are excluded from the randomization part of the study if any of the criteria below are present: - Diagnosis of Myelodysplastic syndrome (MDS). - Diagnosis of Juvenile myelomonocytic leukemia (JMML). - History of previous malignancy (AML diagnosed as secondary cancer). - Known diagnosis of Fanconi anemia. - Prior autologous or allogeneic hematopoietic stem cell transplant. - Planned prophylactic DLI or other immunotherapy interventions after HCT that are not included in the upfront protocol, - Planned anti-leukemic medication after HCT that are not included in the upfront protocol - Known intolerance to any of the chemotherapeutic drugs in the protocol. - Major organ failure precluding administration of planned chemotherapy. - Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment. - Severe concomitant disease that does not allow treatment according to the protocol at the investigator’s discretion; e.g. malformation syndromes, cardiac malformations, metabolic disorders, renal impairment (<30% of normal glomerular filtration rate), severe pulmonary, hepatic or cardiac impairment due to toxicity or infection. - Karnofsky / Lansky score < 50% - Females who are pregnant (positive serum or urine ßHCG) or breastfeeding. - Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation. - Subjects unwilling or unable to comply with the study procedures Exclusion criteria for the observational part of the study Patients are excluded from the observational part of the study if any of the criteria below are present: - Diagnosis of Myelodysplastic syndrome (MDS). - Diagnosis of Juvenile myelomonocytic leukemia (JMML). - Age above 21 years at time of transplantation - No consent is given - Prior autologous or allogeneic hematopoietic stem cell transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives: To investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year GvHD- and relapse-free survival than a conditioning regimen combining three alkylating agents (BuCyMel);Secondary Objective: Exploratory objectives of the randomized part of the study 1) To compare the following outcomes between the 2 arms of the trial: - neutrophil and platelet engraftment, - rate of primary and secondary graft failure, - cumulative incidence of disease relapse, - cumulative incidence of transplant-related mortality, - disease-free and overall survival, - incidence of grade II-IV and III-IV acute GVHD, - incidence of chronic GVHD, - rates of Grade = 3 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, - incidence of infections, - immunological recovery. - quality of life, - late effects, - nutritional status. 2) To analyze the association between pre-HCT Minimal Residual Disease and incidence of relapse, disease-free survival, and overall survival. Exploratory objectives of the observational part of the study 1) To estimate outcomes as above 2) To analyze the association as above;Primary end point(s): The primary endpoint is the 2-year acute grade III to IV-free, chronic non-limited GVHD-free, relapse free survival (GRFS) measured from the time of HCT to the first event (acute GvHD III-IV, chronic non-limited GvHD, relapse, death) or last follow-up. ;Timepoint(s) of evaluation of this end point: 2 years after transplantation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory endpoints: Exploratory endpoints in both interventional and observational parts of the study are as follows: - Disease free Survival (DFS) - Overall Survival (OS) - Cumulative incidence of relapse (CIR) - Transplant-related Mortality (TRM) - Hematologic Recovery - Graft Failure (GF) - Immune Reconstitution. - Acute GVHD - Chronic GVHD - Infections - Toxicity - Transplant-associated hormonal and gonadal late effects - Nutritional status;Timepoint(s) of evaluation of this end point: Between 30 days and two years after transplantation | — |
Countries
Belgium, Denmark, Finland, Hong Kong, Israel, Lithuania, Netherlands, Norway, Spain, Sweden
Contacts
Public ContactMonica Hjalmar
Västra Götalands Regionen
Outcome results
None listed