Mafosfamide in Treating Patients With Progressive or Refractory Meningeal Tumors
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
OBJECTIVES:
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Determine the qualitative and quantitative toxicity of mafosfamide in patients with progressive or refractory meningeal malignancy.
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Determine the maximum tolerated dose of this drug in these patients.
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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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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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
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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
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Meningeal malignancy must be progressive or refractory to conventional therapy
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Meningeal malignancies secondary to an underlying solid tumor are allowed at initial diagnosis provided there is no conventional therapy
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No concurrent bone marrow relapse in leukemia or lymphoma patients
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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
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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:
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception during and for 6 months after study
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No clinically significant metabolic parameter abnormalities (e.g., electrolytes, calcium, and phosphorus)
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No significant systemic illness (e.g., infection)
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Recovered from prior immunotherapy
Chemotherapy:
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At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine (liposomal)) and recovered
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Concurrent systemic chemotherapy to control systemic or bulk CNS disease allowed with the following exceptions:
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No phase I agent
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No agent that significantly penetrates the CNS (e.g., high-dose systemic methotrexate (more than 1 g/m2), high-dose cytarabine (more than 2 g/m2), IV mercaptopurine, fluorouracil, topotecan, or thiotepa)
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No agent known to have serious unpredictable CNS side effects
Endocrine therapy:
- Not specified
Radiotherapy:
-
See Disease Characteristics
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Recovered from prior radiotherapy
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At least 8 weeks since prior craniospinal irradiation
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Local radiotherapy for symptomatic or bulky CNS disease must be given prior to induction therapy
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No concurrent whole brain or craniospinal irradiation
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Concurrent partial brain (e.g., base of brain) or limited-field spinal radiotherapy for asymptomatic bulky (radiographically visible) CNS disease allowed
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Total CNS radiotherapy dose must not exceed accepted safe tissue tolerances
Surgery:
- Not specified
Other:
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At least 1 week since any prior CNS therapy
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At least 7 days since prior intrathecal investigational agent
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At least 14 days since prior systemic investigational agent
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No other concurrent intrathecal or systemic investigational agent
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No other concurrent intrathecal or systemic therapy to treat meningeal malignancy
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No other concurrent intrathecal therapy or agent that significantly penetrates the blood-brain barrier
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No concurrent agent known to have serious unpredictable CNS side effects
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027-0700 |
| 2 | Children's National Medical Center | Washington | District of Columbia | United States | 20010-2970 |
| 3 | Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda | Maryland | United States | 20892-1182 |
| 4 | Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 5 | Mayo Clinic Cancer Center | Rochester | Minnesota | United States | 55905 |
| 6 | Texas Children's Cancer Center | Houston | Texas | United States | 77030-2399 |
| 7 | University of Texas - MD Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
| 8 | Neurological Research Center, Inc. | Bennington | Vermont | United States | 05201 |
| 9 | Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | United States | 98105 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Study Chair: Susan M. Blaney, MD, Texas Children's Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000069240
- NCI-90-C-0095K
- BCM-H-3241