Know Cancer

forgot password

Phase I Study of Intrathecal Mafosfamide

Phase 1
3 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase I Study of Intrathecal Mafosfamide


- 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.

Inclusion Criteria


- 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



- Over 3

Performance status:

- ECOG 0-2

Life expectancy:

- At least 8 weeks


- Not specified


- No clinically significant liver function abnormalities


- No clinically significant renal function abnormalities


- 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)


Biologic therapy:

- Recovered from prior immunotherapy


- 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


- 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

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


- Not specified


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Susan M. Blaney, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Texas Children's Cancer Center


United States: Federal Government

Study ID:




Start Date:

January 2002

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • leptomeningeal metastases
  • Meningeal Neoplasms
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Texas Children's Cancer Center Houston, Texas  77030-2399
Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan  48202
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182
Neurological Research Center, Inc. Bennington, Vermont  05201