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Topotecan Hydrochloride in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment

A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00005811
Enrollment
77
Registered
2003-01-27
Start date
2000-04-30
Completion date
2009-02-28
Last updated
2013-02-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Diffuse Mixed Cell Lymphoma, AIDS-related Diffuse Small Cleaved Cell Lymphoma, AIDS-related Immunoblastic Large Cell Lymphoma, AIDS-related Lymphoblastic Lymphoma, AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Primary CNS Lymphoma, AIDS-related Small Noncleaved Cell Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, HIV-associated Hodgkin Lymphoma, Leptomeningeal Metastases, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

Brief summary

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well topotecan hydrochloride works in treating children with meningeal cancer that has not responded to previous treatment

Detailed description

PRIMARY OBJECTIVES: I. Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to central nervous system (CNS) progression, in pediatric patients with recurrent or refractory neoplastic meningitis. II. Determine the safety and toxicity of this regimen in these patients. III. Evaluate the concentration of matrix metalloproteinases (MMPs) in the cerebrospinal fluid (CSF) of these patients. OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs. other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04) INDUCTION: Patients receive topotecan hydrochloride intrathecally (IT) over 5 minutes twice weekly for 6 weeks. CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning 2 weeks after completion of consolidation, patients receive topotecan hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1. After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 14-77 patients will be accrued for this study.

Interventions

DRUGtopotecan hydrochloride

Given IT

OTHERlaboratory biomarker analysis

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No

Inclusion criteria

* Histologically proven refractory leukemia, lymphoma, or other solid tumor thathas overt meningeal involvement (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04) * Definition of meningeal disease: * Leukemia/lymphoma (including acute lymphoblastic leukemia) * CSF cell count greater than 5/mm\^3 AND evidence of blast cells oncytospin preparation or by cytology * Refractory to conventional therapy, including radiotherapy (i.e., in second or greater relapse) * No concurrent bone marrow relapse * Solid tumors (including medulloblastoma) * Presence of tumor cells on cytospin preparation or cytology OR presence ofmeningeal disease on MRI scans * No clinical evidence of obstructive hydrocephalus or compartmentalization ofCSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPAflow study * If CSF flow block is demonstrated, focal radiotherapy must be administered tosite of block to restore flow and a repeat CSF flow study must show clearing of blockage * No ventriculoperitoneal or ventriculoatrial shunt unless: * Patient is shunt independent and there is evidence that the shunt is nonfunctional * CSF flow study demonstrates normal flow * No impending cord compression, CNS involvement requiring local radiotherapy(e.g., optic nerve), or isolated bulky ventricular or leptomeningeal basedlesions * Performance status - Lansky 50-100% (age 10 and under) * Performance status - Karnofsky 50-100% (over age 10) * At least 8 weeks * Platelet count greater than 40,000/mm\^3 (transfusions allowed) * Bilirubin less than 2.0 mg/dL * SGPT less than 5 times normal * Creatinine less than 1.5 mg/dL * Electrolytes, calcium, and phosphorus normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No significant illness (e.g., uncontrolled infection, except HIV \[i.e., AIDS-related lymphomatous meningitis\]) * Prior immunotherapy allowed and recovered * At least 3 weeks since systemic CNS directed chemotherapy (6 weeks for nitrosoureas) and recovered * At least 1 week since prior intrathecal (IT) chemotherapy (2 weeks for cytarabine \[liposomal\]) * No prior IT chemotherapy on days -14 to -7 before study entry unless evidence of disease progression (e.g., increasing WBC and percentage blasts in patients with leukemia/lymphoma or increased leptomeningeal enhancements in patients with solid tumors) (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04) * Concurrent chemotherapy to control systemic disease or bulk CNS disease allowed if the systemic chemotherapy is not a phase I study agent that significantly penetrates the CSF (e.g., high-dose systemic methotrexate \[greater than 1 g/m\^2\], thiotepa, high-dose cytarabine, temozolomide, IV mercaptopurine, nitrosourea, or topotecan) or an agent known to have serious unpredictable CNS side effects * Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy regimen * See Disease Characteristics * At least 8 weeks since prior cranial irradiation and recovered * No concurrent whole brain or craniospinal irradiation * At least 7 days since prior investigational drug * Time period should be extended if patient has received any investigational agent that is known to have delayed toxic effects after 7 days or a prolonged half-life * No other concurrent investigational agents * No concurrent therapy (IT or systemic) for leptomeningeal disease * No other concurrent systemic agents that significantly penetrate the blood-brain barrier

Design outcomes

Primary

MeasureTime frame
For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10Up to 54 months
For the patients with solid tumors, a proportion of patients who do not experience an event, defined to be death, progressive disease, relapse, or second malignancy of less than 0.3Up to 54 months
Safety and toxicityUp to 54 months
Concentration of matrix metalloproteinases in the CSFUp to 54 months

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026