Christina Peters, Prof. MD PhD Study Chair St. Anna Kinderspital, Vienna, Austria Peter Bader, Prof. MD PhD Study Chair Klinik für Kinder- u. Jugendheilkunde III, Johann Wolfgang Goethe Universität, Frankfurt, Germany Franco Locatelli, Prof. MD PhD Study Chair Department of Pediatric Hematology and Oncology IRCCS Ospedale, Rome, Italy Marc Ansari, MD, PD Principal Investigator Département de Pédiatrie, Hôpital Cantonal de Genève
1. Genetic variants in participants as a marker of risk of Adverse events and/or Efficacy of the studied agents (Time Frame - through study completion, an average of 2 years): Genotyping of candidates genes related to pharmacokinetics and pharmacodynamics of the studied agents.
Association study between the herein genetic variants and the below mentioned phenotypes (odd ratio).
Secondary outcome:
1. Number of participants with acute Graft-versus-host disease (aGvHD) according to the Glucksberg scale and Seattle criteria (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years)
2. Number of participants with chronic Graft-versus-host disease (cGvHD) according to the Glucksberg scale and Seattle criteria (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years)
3. Number of participants with VOD/SOS according to the Seattle criteria (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years)
4. Number of participants with Neutrophil recovery as a measure of Safety and Tolerability (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): defined as the first of 3 consecutive days with an absolute neutrophil count of 0.5x10^9/L or higher
5. Number of participants with Platelet recovery as a measure of Safety and Tolerability (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): Defined as the first of 3 consecutive days with platelet counts higher that 20x10^9/L without transfusion
6. Number of participants with Primary graft failure or rejection as a measure of Safety and Tolerability (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): Defined by persistent pancytopenia with no evidence of hematologic recovery of donor cells beyond 28 days after transplantation, and secondary graft failure by a rapid decrease in neutrophil count after successful engraftment
7. Transplant related mortality (TRM) (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): the time of transplant until all causes of death after transplant not related to relapse
8. Event free survival (EFS) (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): the time of transplant until death, relapse or graft failure, whichever occurs first.
9. Overall survival (OS) (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years): the time between transplantation and death due to any causes
10. Cumulative incidence of relapse (Time Frame - 18 months after inclusion of first patient, afterwards, annually up to 10 years)
Experimental: Total body irradiation (TBI) The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses.
Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.
Experimental: Busulfan The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses.
Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.
Experimental: Treosulfan The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses.
Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.
Pharmacogenomics (DNA analyses): Blood samples (2x5ml EDTA tubes) should be collected just before the start of the conditioning regimen from every patient regardless of therapeutic arm by every centre and stored ≤-20°C Patient should be in remission (MRD negative) for this sampling, otherwise the sample should be taken using a mouth swab/saliva (not intravenously).
For second transplant patients, please provide DNA taken before first transplant or a fresh saliva samples.
Busulfan plasma level measurements: Bu PK analysis after the first dose of IV Bu (+potential subsequent ones).
Blood sampling:
->For Bu 4 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 15 min (Time 2), 30 min (Time 3), 1 hour (Time 4) and 4 hour (Time 5) after the end of infusion
->For Bu 1 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 1 hour (Time 2), 3 hour (Time 3), 5 hour (Time 4), 7 hour (Time 5) and 11 hour (Time 6) after the end of infusion.
For centers not performing BU TDM, perform Dried Blood Sampling (DBS) analysis:
-> 0.5ml blood sample should be collected and 5µl spotted onto DBS cards in duplicate. Dry them max 5 hours and then keep in a sealed envelope and store at -80°C, as below
Quelle: ClinicalTrials.gov
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