A Phase I Trial of Tomudex in Children With Leukemia
I. Determine the maximum tolerated dose and dose limiting toxicity of raltitrexed given for
three weeks to children with refractory acute leukemia.
II. Determine the incidence and severity of other toxic effects of this regimen in these
III. Determine a safe and tolerable dose of raltitrexed, administered in this manner, to be
used in phase II studies.
IV. Determine the pharmacokinetics of this regimen in these patients. V. Determine if plasma
2' deoxyuridine concentrations are associated with raltitrexed toxicity or pharmacokinetics.
VI. Evaluate the antitumor activity of raltitrexed against recurrent leukemia.
OUTLINE: This is a dose escalation study.
Patients receive raltitrexed intravenously over 15 minutes once weekly for 3 weeks followed
by 1 week of rest. Treatment continues in the absence of disease progression and
In the absence of dose-limiting toxicity (DLT) in the first cohort of 6 patients treated,
subsequent cohorts of 6 patients each receive escalating doses of raltitrexed on the same
schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation
ceases and the next lower dose is declared the maximum tolerated dose.
Patients are followed every 6 months for 4 years, then annually thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD based on incidence of DLT graded according to CTC version 2.0
Up to 4 weeks
Steven D. Weitman
Swiss Pediatric Oncology Group - Geneva
United States: Food and Drug Administration