Raltitrexed in Treating Children With Refractory Acute Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003528
First received: November 1, 1999
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Drug: raltitrexed
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Tomudex in Children With Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD based on incidence of DLT graded according to CTC version 2.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: September 1998
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • D1694
  • ICI-D1694
  • TDX
  • Tomudex

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003528

Locations
Switzerland
Swiss Pediatric Oncology Group - Geneva
Geneva, Switzerland, 1205
Sponsors and Collaborators
Investigators
Principal Investigator: Steven D. Weitman Swiss Pediatric Oncology Group - Geneva
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003528     History of Changes
Other Study ID Numbers: NCI-2012-01839, 9779, U01CA097452, CDR0000066575
Study First Received: November 1, 1999
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Raltitrexed
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Folic Acid Antagonists
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014