Trial | NCT00003528  Report issue

Title

Raltitrexed in Treating Children With Refractory Acute Leukemia
A Phase I Trial of Tomudex in Children With Leukemia

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    30
Phase I trial to study the effectiveness of raltitrexed in treating children with refractory acute leukemia. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
OBJECTIVES:

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 patients.

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.
Study Started
Sep 30
1998
Primary Completion
Jun 30
2002
Last Update
Jan 16
2013
Estimate

Drug raltitrexed

Given IV

  • Other names: D1694, ICI-D1694, TDX, Tomudex

Arm I Experimental

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.

Criteria 

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
No Results Posted