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A Phase I Dose Escalation Study of Intrathecal DepoFoam Encapsulated Cytarabine (DTC 101) in Pediatric Patients With Advanced Meningeal Malignancies


Phase 1
1 Year
21 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Phase I Dose Escalation Study of Intrathecal DepoFoam Encapsulated Cytarabine (DTC 101) in Pediatric Patients With Advanced Meningeal Malignancies


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.

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.

Inclusion 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

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

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

John E. Gait, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Pacira Pharmaceuticals, Inc

Authority:

United States: Federal Government

Study ID:

CDR0000065754

NCT ID:

NCT00003073

Start Date:

February 1997

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Leukemia
  • Lymphoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • unspecified childhood solid tumor, protocol specific
  • recurrent/refractory childhood Hodgkin lymphoma
  • leptomeningeal metastases
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • Leukemia
  • Lymphoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location
Stanford University Medical Center Stanford, California  94305-5408
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Texas Children's Cancer Center Houston, Texas  77030-2399
University of Texas Southwestern Medical Center at Dallas Dallas, Texas  75235-8897