Phase I Trial of Intrathecal Liposomal Cytarabine in Children With Neoplastic Meningitis

Abstract

The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.

Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

“…Liposomal cytarabine has been used only in the therapeutic setting both for HIV 31 and in the general population. [24][25][26][27][28][29][30] In particular, the only study of the treatment of lymphomatous meningitis in 5 patients with HIV-NHL showed a 60% CR rate. 31 There is only limited experience in the prophylactic setting in patients with aggressive lymphoma in the general population, whereas some data have been published in patients with acute lymphocytic or myeloid leukemia.…”

“…Liposomal cytarabine was administered at the standard dose of 50 mg [24][25][26][27][28][29][30][31] by lumbar sac injection on Day 1 of the systemic treatment. The use of intrathecal steroids was not allowed.…”

“…16,17,20 Recently, a liposomal formulation of cytarabine (DepoCyte) has shown similar activity of free cytarabine, with a lower toxicity profile and a more convenient dosing regimen in the treatment of both lymphomatous meningitis and meningitis from solid tumors. [24][25][26][27][28][29][30] Up to now, there are no data on the efficacy and safety of liposomal cytarabine in the prophylaxis of CSF recurrence or progression in HIV-positive patients, although it has been used in the therapeutic setting. 31 With the aim of evaluating the feasibility and activity of liposomal cytarabine in the setting of prophylaxis in HIV-related NHL, from May 2006 to December 2008 we started a phase 2 prospective study at the National Cancer Institute in Aviano, Italy.…”

“…The incidence of headache in our study was similar to that reported in all published studies of liposomal cytarabine in the treatment of lymphomatous meningitis. [24][25][26][27][28][29][30] The other side effects were negligible. Up to now, with a median follow-up of 10.5 months, only 1 (3%) patient with Burkitt lymphoma, who did not receive all the planned injections, has developed disease recurrence in the CSF after 12 months from the end of the treatment.…”

Safety of liposomal cytarabine CNS prophylaxis in children, adolescent and young adult hematopoietic stem cell transplant recipients with acute leukemia and non-Hodgkin lymphoma

“…Liposomal cytarabine is a sustained release liposomal formulation of cytarabine approved for IT or intraommaya treatment of recurrent lymphomatous meningitis that allows for sustained release of cytarabine with prolonged therapeutic concentration and thus prolonged drug exposure of up to 8 days in children and 14 days in adults. [2][3][4] The use of liposomal cytarabine could potentially overcome some of the barriers to post-HSCT administration of CNS prophylaxis and may provide for improved outcome results. The primary objectives of this single-institution study were to determine the safety and tolerability of liposomal cytarabine as prophylaxis prior to and following HSCT in pediatric recipients with acute leukemia and non-Hodgkin lymphoma at risk of CNS recurrence post HSCT.…”