mafosfamide in treating patients with progressive or refractory meningeal tumors

Conditions: Brain and Central Nervous System Tumors

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.

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.

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

Keywords: leptomeningeal metastases