Raltitrexed in Treating Children With Refractory Acute Leukemia

A Phase I Trial of Tomudex in Children With Leukemia

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

Study Overview

• Status: Completed
• Conditions: Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia
• Intervention / Treatment: Drug: raltitrexed

Detailed Description

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Swiss Pediatric Oncology Group - Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; 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.	Drug: raltitrexed; Given IV; Other Names: Tomudex; D1694; ICI-D1694; TDX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD based on incidence of DLT graded according to CTC version 2.0	Up to 4 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven D. Weitman, Swiss Pediatric Oncology Group - Geneva

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): June 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: February 27, 2004
• First Posted (Estimate): March 1, 2004

Study Record Updates

• Last Update Posted (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, Lymphoid; Leukemia; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folic Acid Antagonists; Raltitrexed
• Other Study ID Numbers: NCI-2012-01839; U01CA097452 (U.S. NIH Grant/Contract); 9779; CDR0000066575 (Registry Identifier: PDQ (Physician Data Query))