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 study the effectiveness of liposomal cytarabine in treating young patients who have recurrent or refractory meningeal leukemia, lymphoma, or solid tumors.

Condition	Treatment or Intervention	Phase
leptomeningeal metastases recurrent childhood large cell lymphoma recurrent childhood acute myeloid leukemia childhood diffuse large cell lymphoma recurrent childhood small noncleaved cell lymphoma unspecified childhood solid tumor, protocol specific recurrent childhood lymphoblastic lymphoma childhood immunoblastic large cell lymphoma recurrent childhood acute lymphoblastic leukemia recurrent/refractory childhood Hodgkin's disease	Procedure: chemotherapy  Drug: cytarabine (liposomal)	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the qualitative or quantitative toxic effects and tolerability of liposomal cytarabine (Depofoam encapsulated cytarabine; DTC 101) in pediatric patients with recurrent or refractory meningeal malignancies. II. Define a safe dose of DTC 101 in these patients for future clinical studies. III. Determine the plasma and CSF pharmacokinetics of DTC 101 in these patients.

PROTOCOL OUTLINE: This is a dose escalation, multicenter study. Patients are placed in one of three age-related strata: stratum 1, 3 to 21 years of age; stratum 2, at least 2 but less than 3 years of age; stratum 3, at least 1 but less than 2 years of age. Patients receive an induction dose of intrathecal liposomal cytarabine (Depofoam encapsulated cytarabine; DTC 101) administered once every 2 weeks for 2 courses. Patients who have achieved a partial response or received significant clinical benefit with stable disease may receive a third induction dose of DTC 101, 2 weeks following the second dose. In the absence of progressive disease, patients can proceed to consolidation therapy. During consolidation therapy, intrathecal DTC 101 is administered once every 4 weeks for 2 courses, beginning 4 weeks after the last induction dose. Patients experiencing a complete or significant response can proceed to maintenance therapy. Patients receive a maintenance dose of intrathecal DTC 101 once every 8 weeks for a total of 6 doses, beginning 4 weeks after the second consolidation dose. At least 3 patients are evaluated at each dose level. Dose escalation to the next level proceeds when a minimum of 3 patients per cohort has successfully completed induction therapy and been evaluated. Patients will be followed at 1, 2, 3, 6, 9, and 12 months post treatment, until relapse or death.

PROJECTED ACCRUAL: A minimum of 12-15 patients will be accrued for each stratum over 18 to 24 months.

Ages Eligible for Study:  1 Year   -   21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven recurrent or refractory leukemia, lymphoma, or other solid tumor that has overt meningeal involvement
• Definition of meningeal disease: Leukemia/lymphoma: CSF cell count at least 5/mm3 and evidence of blast cells on cytospin preparation or cytology; Solid tumors: Presence of tumor cells on cytospin preparation or cytology OR evidence of meningeal disease on CT or MRI scan
• No bone marrow disease

--Prior/Concurrent Therapy--

• Biologic therapy: No acute toxic effects from prior immunotherapy; No prior allogeneic or autologous bone marrow transplantations within 3 months of study
• Chemotherapy: No prior systemic CNS directed chemotherapy within 3 weeks of study; No prior nitrosourea within 6 weeks of study; No prior intrathecal chemotherapy within 1 week of study; No acute toxic effects from prior chemotherapy; No prior DTC 101; Concurrent systemic chemotherapy for management of primary cancer allowed; Concurrent dexamethasone with systemic chemotherapy regimen allowed; No concurrent chemotherapy for leptomeningeal disease; No concurrent high dose methotrexate, high dose cytarabine, mercaptopurine, thiotepa, fluorouracil, and topotecan
• Endocrine therapy: Concurrent prednisone therapy with systemic chemotherapy allowed
• Radiotherapy: No prior craniospinal irradiation within 8 weeks of study; No acute toxic effects from prior radiotherapy; Concurrent local radiation therapy allowed; No concurrent whole brain or craniospinal radiotherapy
• Surgery: Not specified
• Other: At least 2 weeks since investigational drugs and recovered; No other concurrent investigational drugs; Concurrent antibiotic therapy allowed

--Patient Characteristics--

• Age: 1 to 21
• Performance Status: ECOG 0-2
• Life Expectancy: At least 8 weeks
• Hematopoietic: Platelet count greater than 40,000/mm3
• Hepatic: Bilirubin less than 2.0 mg/dL; ALT less than 5 times upper limit of normal
• Renal: Creatinine less than 1.5 mg/dL
• Other: Not pregnant or nursing; Negative pregnancy test; Effective contraceptive method used by fertile patients; No uncontrolled illness or infection (except for HIV positive patients); No obstructive hydrocephalus or compartmentalization of the CSF flow

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
Texas
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States
      University of Texas Southwestern Medical Center at Dallas, Dallas,  Texas,  75235-8897,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
Canada, Alberta
      Alberta Children's Hospital, Calgary,  Alberta,  T2T 5C7,  Canada

Study chairs or principal investigators

John E. Gait,  Study Chair,  SkyePharma   

Study ID Numbers:  CDR0000065754; SKYEPHARMA-96-002; NCI-V97-1336; DTC-96-002
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003073
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08