FLUDARABINE PHOSPHATE for Hematological malignancy | Allogeneic haematopoietic stem cell transplantation (reduced-intensity conditioning)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years\n- Be able to understand and sign an informed consent\n- Hematological malignancy\n- Women of childbearing potential (WOCBP), defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal, and men who are sexually active must use a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for participants participating in clinical trials. Men must use a highly effective method of birth control and agree not to father a child or donate sperm during and after the study. For females, these restrictions apply for 6 months after chemotherapy/conditioning. For males, these restrictions apply for 6 months after chemotherapy/conditioning\n- Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning regimen containing IV Fludarabine 30 mg/m² for 5 days, IV Melphalan 100 or 140 mg/m² in total and IV ATG (Thymoglobulin or Grafalon according to local standard protocol)\n- Use of Tacrolimus or Ciclosporin and Mycophenolate Mofetil (MMF) as graft versus host disease (GvHD) prevention\n- Human leukocyte antigen (HLA) identical sibling donor, 10/10 HLA matched unrelated donor or 9/10 mismatched unrelated donor"}

Exclusion criteria

• {"criterion_text":"- Any condition not fulfilling inclusion criteria\n- Pregnancy or lactation\n- Known allergic reactions to components of the conditioning regimen (Fludarabine, Melphalan, ATG)\n- No other line available for blood sampling than the infusion line through which Fludarabine was administered (patients with a double or triple lumen central catheter will not be excluded as a second lumen is available for sampling) and patient unable or unwilling to undergo peripheral blood sampling\n- Patients on dialysis\n- Renal insufficiency with creatinine clearance < 30 ml/min\n- Acute or chronic active infection\n- Decompensated hemolytic anemia"}

Primary endpoints

• {"endpoint_text":"- Area under the curve (AUC) of F-Ara-A after exposure to Fludarabine in the context of reduced intensity conditioning with Fludarabine, Melphalan and anti-thymocyte globulin (ATG). To be assessed after the last included patient has finished conditioning regimen.","definition_or_measurement_approach":"Measurement: AUC of plasma F-Ara-A after exposure to Fludarabine; assessment timing stated as 'after the last included patient has finished conditioning regimen.'"}

Secondary endpoints

• {"endpoint_text":"- Association between F-Ara-A AUC and creatinine clearance; To be assessed after the last included patient has finished conditioning regimen","definition_or_measurement_approach":"Association analysis between F-Ara-A AUC and measured creatinine clearance; assessment after last included patient finished conditioning."}
• {"endpoint_text":"- Association between F-Ara-A AUC and bodyweight/BMI; To be assessed after the last included patient has finished conditioning regimen.","definition_or_measurement_approach":"Association analysis between F-Ara-A AUC and bodyweight/BMI; assessment after last included patient finished conditioning."}
• {"endpoint_text":"- Influence of F-Ara-A AUC on non-relapse mortality, relapse rate, progression free survival and overall survival; To be assessed when: - the first 25 included patients have reached 1 year, 2 years and 3 years of follow-up post-transplant. - all included patients have reached 1 year, 2 years and 3 years of follow-up post-transplant.","definition_or_measurement_approach":"Time-to-event analyses (non-relapse mortality, relapse rate, PFS, OS) stratified by F-Ara-A AUC; assessments at 1, 2 and 3 years for first 25 patients and for all patients."}
• {"endpoint_text":"- Influence of F-Ara-A AUC on median time to neutrophil and platelet engraftment; To be assessed when: - the first 25 included patients have reached 1 year of follow-up post-transplant. - all included patients have reached 1 year of follow-up post-transplant.","definition_or_measurement_approach":"Comparison of median time to neutrophil and platelet engraftment by F-Ara-A AUC; assessment at 1 year for first 25 patients and all patients."}
• {"endpoint_text":"- Influence of F-Ara-A AUC on peripheral CD4 and CD8 T-cell count. To be assessed when: - the first 25 included patients have reached 1 year, 2 years and 3 years of follow-up post-transplant. - all included patients have reached 1 year, 2 years and 3 years of follow-up post-transplant.","definition_or_measurement_approach":"Analysis of peripheral CD4/CD8 T-cell counts in relation to F-Ara-A AUC; assessments at 1, 2 and 3 years as specified."}
• {"endpoint_text":"- Influence of F-Ara-A AUC on incidence of central nervous system complications/events in the first year after allogeneic stem cell transplant.","definition_or_measurement_approach":"Incidence comparison of CNS complications/events within first year post-transplant by F-Ara-A AUC."}
• {"endpoint_text":"- Applicability of pharmacokinetic model published by Langenhorst et al (6) on the study population to predict F-Ara-A AUC.","definition_or_measurement_approach":"Validation/applicability analysis of an existing pharmacokinetic model to predict F-Ara-A AUC in this RIC population."}

Belgium

Earliest CTIS Part Ii Submission Date

31-05-2024

Latest Decision Or Authorization Date

18-06-2024

Processing Time Days

18

Number Of Sites

3

Number Of Participants

50

Primary sponsor

Full Name

Universitair Ziekenhuis Gent

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium