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A Phase I Trial of Tomudex in Children With Leukemia

Phase 1
21 Years
Not Enrolling
Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia

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Trial Information

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
unacceptable toxicity.

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.

Inclusion Criteria:

- Histologically or cytologically proven acute leukemia (M3 marrow) that is refractory
to conventional therapy or for which no effective therapy exists

- No CNS leukemia

- No solid tumors

- Performance status: Karnofsky 50-100% OR Lansky at least 50 (for infants)

- Life expectancy: At least 8 weeks

- Bilirubin less than 1.5 mg/dL

- SGPT less than 5 times normal

- Normal creatinine for age OR GFR at least 70 mL/min

- No significant systemic illness such as infection

- No significant third space fluid collection

- Not pregnant or nursing

- Recovered from acute toxic effects of prior immunotherapy

- At least 6 months since prior bone marrow transplant with no evidence of
graft-versus-host disease

- At least 10 days since prior biologic therapy

- At least 1 week since prior growth factors

- At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
and recovered

- No concurrent steroids

- Recovered from acute toxic effects of all prior radiotherapy

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 6 months since prior substantial bone marrow radiation

- No other concurrent anticancer therapy or investigational agents

- No concurrent nonsteroidal anti-inflammatory agents

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD based on incidence of DLT graded according to CTC version 2.0

Outcome Time Frame:

Up to 4 weeks

Safety Issue:


Principal Investigator

Steven D. Weitman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Swiss Pediatric Oncology Group - Geneva


United States: Food and Drug Administration

Study ID:




Start Date:

September 1998

Completion Date:

Related Keywords:

  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid