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Mafosfamide in Treating Patients With Progressive or Refractory Meningeal Tumors

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
mafosfamide
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring leptomeningeal metastases

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Los Angeles
  • Children's National Medical Center
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Josephine Ford Cancer Center at Henry Ford Hospital
  • Mayo Clinic Cancer Center
  • Texas Children's Cancer Center
  • University of Texas - MD Anderson Cancer Center
  • Neurological Research Center, Inc.
  • Children's Hospital and Regional Medical Center - Seattle

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 8, 2002
Last Updated
April 29, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00031928
Brief Title
Mafosfamide in Treating Patients With Progressive or Refractory Meningeal Tumors
Official Title
Phase I Study of Intrathecal Mafosfamide
Study Type
Interventional

2. Study Status

Record Verification Date
November 2003
Overall Recruitment Status
Completed
Study Start Date
January 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
leptomeningeal metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
3000 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
mafosfamide

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan M. Blaney, MD
Organizational Affiliation
Texas Children's Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States
Facility Name
Josephine Ford Cancer Center at Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Neurological Research Center, Inc.
City
Bennington
State/Province
Vermont
ZIP/Postal Code
05201
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

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Mafosfamide in Treating Patients With Progressive or Refractory Meningeal Tumors

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