Mafosfamide in Treating Patients With Progressive or Refractory Meningeal Tumors

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase I Study of Intrathecal Mafosfamide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00031928
• Other study ID #: CDR0000069240
• Secondary ID: NCI-90-C-0095KBC
• Status: Completed
• Phase: Phase 1
• First received: March 8, 2002
• Last updated: April 29, 2015
• Start date: January 2002

Study information

• Verified date: November 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to determine the effectiveness of mafosfamide in treating patients who have progressive or refractory meningeal tumors.

Description:

OBJECTIVES:

• Determine the qualitative and quantitative toxicity of mafosfamide in patients with progressive or refractory meningeal malignancy.

• Determine the maximum tolerated dose of this drug in these patients.

• Determine the cerebrospinal fluid pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive intrathecal mafosfamide over 20 minutes twice weekly for 6 weeks (induction therapy). Patients then receive intrathecal mafosfamide once weekly for 4 weeks (consolidation therapy), twice a month for 4 months, and then monthly thereafter (maintenance therapy) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of mafosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3000 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of leukemia or lymphoma with meningeal involvement defined as cerebrospinal fluid cell count at least 5/mm^3 AND evidence of blast cells on cytospin preparation or by cytology OR

• Diagnosis of other solid tumor with meningeal involvement defined as presence of tumor cells on cytospin preparation or cytology OR presence of measurable meningeal disease on CT or MRI scan

• Meningeal malignancy must be progressive or refractory to conventional therapy

• Meningeal malignancies secondary to an underlying solid tumor are allowed at initial diagnosis provided there is no conventional therapy

• No concurrent bone marrow relapse in leukemia or lymphoma patients

• No clinical evidence of obstructive hydrocephalus or compartmentalization of the cerebrospinal fluid flow as documented by a radioisotope indium In 111 or technetium Te 99-DTPA flow study

• Patients demonstrating restored flow after focal radiotherapy are allowed

PATIENT CHARACTERISTICS:

Age:

• Over 3

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Not specified

Hepatic:

• No clinically significant liver function abnormalities

Renal:

• No clinically significant renal function abnormalities

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after study

• No clinically significant metabolic parameter abnormalities (e.g., electrolytes, calcium, and phosphorus)

• No significant systemic illness (e.g., infection)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Recovered from prior immunotherapy

Chemotherapy:

• At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine (liposomal)) and recovered

• Concurrent systemic chemotherapy to control systemic or bulk CNS disease allowed with the following exceptions:

• No phase I agent

• No agent that significantly penetrates the CNS (e.g., high-dose systemic methotrexate (more than 1 g/m^2), high-dose cytarabine (more than 2 g/m^2), IV mercaptopurine, fluorouracil, topotecan, or thiotepa)

• No agent known to have serious unpredictable CNS side effects

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

• Recovered from prior radiotherapy

• At least 8 weeks since prior craniospinal irradiation

• Local radiotherapy for symptomatic or bulky CNS disease must be given prior to induction therapy

• No concurrent whole brain or craniospinal irradiation

• Concurrent partial brain (e.g., base of brain) or limited-field spinal radiotherapy for asymptomatic bulky (radiographically visible) CNS disease allowed

• Total CNS radiotherapy dose must not exceed accepted safe tissue tolerances

Surgery:

• Not specified

Other:

• At least 1 week since any prior CNS therapy

• At least 7 days since prior intrathecal investigational agent

• At least 14 days since prior systemic investigational agent

• No other concurrent intrathecal or systemic investigational agent

• No other concurrent intrathecal or systemic therapy to treat meningeal malignancy

• No other concurrent intrathecal therapy or agent that significantly penetrates the blood-brain barrier

• No concurrent agent known to have serious unpredictable CNS side effects

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• mafosfamide

Locations

Country	Name	City	State
United States	Neurological Research Center, Inc.	Bennington	Vermont
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,