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

NCT ID: NCT00005811

Last Updated: 2013-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-04-30
• Study Completion Date: 2009-02-28

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (topotecan hydrochloride)

INDUCTION: Patients receive topotecan hydrochloride 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.

Group Type: EXPERIMENTAL

topotecan hydrochloride

Intervention Type: DRUG

Given IT

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

topotecan hydrochloride

Given IT

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

hycamptamine; Hycamtin; SKF S-104864-A; TOPO

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Blaney

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Arcadia, California, United States

Countries

United States

Other Identifiers

P9962

Identifier Type: -

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067813

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01848

Identifier Type: -

Identifier Source: org_study_id

NCT00013676

Identifier Type: -

Identifier Source: nct_alias