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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005811
First received: June 2, 2000
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
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
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10 [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
  • 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 0.3 [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
  • Safety and toxicity [ Time Frame: Up to 54 months ] [ Designated as safety issue: Yes ]
  • Concentration of matrix metalloproteinases in the CSF [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]

Enrollment: 77
Study Start Date: April 2000
Study Completion Date: February 2009
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: topotecan hydrochloride
Given IT
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005811

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Susan Blaney Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005811     History of Changes
Obsolete Identifiers: NCT00013676
Other Study ID Numbers: NCI-2012-01848, P9962, U10CA098543, CDR0000067813
Study First Received: June 2, 2000
Last Updated: February 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lymphoma
Lymphoma, Non-Hodgkin
Medulloblastoma
Neoplasm Metastasis
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Meningeal Neoplasms
Meningeal Carcinomatosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on August 21, 2014