Cumulative exposure to Fludarabine in patients undergoing reduced intensity allogeneic stem cell transplantation in Belgium

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Gent

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

4 Jun 2025 → ongoing

Decision date (initial)

2024-06-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Department of Hematology Ghent University Hospital

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response

The cumulative exposure and interpatient variability in (cumulative) exposure to F-Ara-A in patients receiving reduced intensity conditioning (RIC) with standard dose Fludarabine based on body surface area (BSA).

Secondary objectives 4

1. Impact of patient covariates on cumulative exposure to Fludarabine
2. Impact of F-Ara-A exposure on long-term patient outcome
3. Impact of F-Ara-A exposure on neurological toxicity
4. Validate a previously published pharmacokinetic model of F-Ara-A (developed in myeloablative conditioning (MAC) setting) in RIC setting

Conditions and MedDRA coding

Patients undergoing allogeneic HSCT, for hematological malignancy, following RIC with Fludarabine, Melphalan and ATG.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years
2. Be able to understand and sign an informed consent
3. Hematological malignancy
4. 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
5. 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)
6. Use of Tacrolimus or Ciclosporin and Mycophenolate Mofetil (MMF) as graft versus host disease (GvHD) prevention
7. Human leukocyte antigen (HLA) identical sibling donor, 10/10 HLA matched unrelated donor or 9/10 mismatched unrelated donor

Exclusion criteria 8

1. Any condition not fulfilling inclusion criteria
2. Pregnancy or lactation
3. Known allergic reactions to components of the conditioning regimen (Fludarabine, Melphalan, ATG)
4. 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
5. Patients on dialysis
6. Renal insufficiency with creatinine clearance < 30 ml/min
7. Acute or chronic active infection
8. Decompensated hemolytic anemia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 7

1. Association between F-Ara-A AUC and creatinine clearance; To be assessed after the last included patient has finished conditioning regimen
2. Association between F-Ara-A AUC and bodyweight/BMI; To be assessed after the last included patient has finished conditioning regimen.
3. 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.
4. 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.
5. 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.
6. Influence of F-Ara-A AUC on incidence of central nervous system complications/events in the first year after allogeneic stem cell transplant.
7. Applicability of pharmacokinetic model published by Langenhorst et al (6) on the study population to predict F-Ara-A AUC.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Gent

Sponsor organisation

Universitair Ziekenhuis Gent

Address

Corneel Heymanslaan 10

City

Gent

Postcode

9000

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Anke Delie

Public contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Anke Delie

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications