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Prospective study of therapeutic drug monitoring on the Busulfan-Thiotepa Regimen for Autologous Transplantation in Central Nervous System Malignant Lymphoma. (TDMB study)

Safety verification of therapeutic drug monitoring for Busulfan

Hattori Keiichiro

University of Tsukuba Hospital

2-1-1 Amakubo,Tsukuba,Ibaraki

hattori.keiichiro.fu@u.tsukuba.ac.jp

Hattori Keiichiro

University of Tsukuba Hospital

2-1-1 Amakubo,Tsukuba,Ibaraki

+81-29-853-3127

hattori.keiichiro.fu@u.tsukuba.ac.jp

Recruiting

June. 02, 2026

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

This study is intended for patients who meet all of the following criteria.
1) Have completed haematopoietic stem cell collection for ASCT
2) Are aged 18 years or older at the time of consent
3) Have demonstrated a reduction in central nervous system lesions of at least partial response (PR) on a brain MRI performed within 28 days of registration, compared to the time of diagnosis
4) Have an ECOG PS of 0-2 as assessed within 14 days of registration
5) Patients who meet all of the following criteria based on tests conducted within 14 days prior to registration
AST and ALT are 3 times or less the upper limit of the facility's reference range
gammaGTP is 2.5 times or less the upper limit of the facility's reference range
Total bilirubin is 1.5 times or less the facility's reference range
Creatinine is 1.5 times or less the facility's reference range
6) Patients whose left ventricular ejection fraction (LVEF) was 50% or higher in a cardiac ultrasound examination performed within 56 days prior to registration
7) Patients who, after receiving a full explanation regarding participation in this trial and having fully understood the details, have provided written informed consent of their own free will

Patients meeting any of the following criteria will be excluded from the study.
1) Patients with intraocular CNSL without brain lesions
2) Patients with a pathological diagnosis of CNSL other than B-cell tumours
3) Patients who have received any treatment (other than haematopoietic stem cell collection) for the primary disease within 14 days of registration
4) Patients who have undergone ASCT within 6 months of registration
5) Patients who have received a live vaccine within 84 days of registration
6) Patients with concurrent malignancies
7) Pregnant or breastfeeding patients
8) Patients with poorly controlled infections
9) Patients with poorly controlled diabetes
10) Patients who have received other investigational drugs or clinical trial drugs within 3 months prior to the start of administration of the study drug
11) Other patients deemed unsuitable as subjects by the principal (or co-) investigator

Both

Central nervous system lymphoma

Administer busulfan at a dose of 3.2 mg/kg/day as a pre-treatment. The decision on whether to administer additional doses on days 3 and 4 is based on the cumulative AUC of busulfan on day 1 (day 1 AUC); the dose on day 2 is administered regardless of the AUC. If the Day 1 AUC is 30 mg*h/L or higher, no additional doses are administered up to Day 2 (Bu6.4); if the Day 1 AUC is 20 mg*h/L or higher but less than 30 mg*h/L, additional doses are administered up to Day 3 (Bu9.6); if the Day 1 AUC is less than 30 mg*h/L, additional doses are administered on both Days 3 and 4 (Bu12.8).

The occurrence of Grade 3 or higher liver dysfunction, for which a causal relationship with the administration of busulfan cannot be ruled out.

1) Pharmacokinetic evaluation of Busulfan (AUC, PK parameters [T1/2, Cmax, Cmean, CL, Vd], trough levels on the day of the first and final Busulfan doses)
2) Presence or absence of recurrence at the end of the observation period, non-recurrence mortality rate, overall survival rate
3) Presence or absence of the GSTA1*B (variant) genetic polymorphism
4) Presence or absence of the ABCB1 genetic polymorphism rs1045642 (c.3435c>t)
5) Complete blood count, general biochemical tests, electrolytes, blood glucose levels
6) Adverse events other than liver dysfunction

+81-29-853-3749

May. 20, 2026

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