Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor

NCT ID: NCT00003273

Last Updated: 2015-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

1997-11-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed brain tumor.

Detailed Description

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OBJECTIVES:

* Investigate the toxicity of and response rate to an intensification of an induction chemotherapy regimen (regimen A: cisplatin, vincristine, cyclophosphamide, and etoposide) by incorporation of high-dose methotrexate with leucovorin calcium rescue in patients with primitive neuroectodermal tumors and evidence of leptomeningeal dissemination (M1, M2, or M3).
* Investigate the toxicity of and response rate to a new dose intensive induction chemotherapy regimen (regimen C: vincristine, carboplatin, and temozolomide) in children under ten years of age who are newly diagnosed with either high grade gliomas or diffuse intrinsic pontine tumors. (Regimen B closed to accrual effective 3/30/2000; regimen C open to accrual effective 7/21/2000)
* Investigate the feasibility of utilizing regimen C chemotherapy followed by consolidation with myeloablative chemotherapy and autologous stem cell (either bone marrow and/or peripheral blood) rescue in these patients. (Regimen B closed to accrual effective 3/30/2000; regimen C open to accrual effective 7/21/2000)
* Investigate the toxicity of and response rate to an intensification of induction regimen A chemotherapy by incorporation of high-dose methotrexate with leucovorin calcium rescue in patients with primitive neuroectodermal tumors and evidence of leptomeningeal dissemination (M1, M2, or M3).
* Estimate the time to disease progression and the pattern of relapse in patients who do not have radiographic or cytologic evidence of residual disease at the time of consolidation chemotherapy and who, therefore, do not receive post consolidation irradiation.
* Estimate the time to disease progression and the pattern of relapse in patients who have radiographic or cytologic evidence of residual disease at the time of consolidation chemotherapy and who, therefore, receive post consolidation irradiation.
* Assess the morbidity and mortality of the consolidation chemotherapy regimen following either regimen C or the intensified regimen A in these patients. (Regimen B closed to accrual effective 3/30/2000; regimen C open to accrual effective 7/21/2000)
* Assess the impact that irradiation avoidance or the administration of reduced volume craniospinal and/or focused field local irradiation has on neuropsychometric, endocrinological functions, and physical growth.

OUTLINE: This is a two regimen study based on disease characteristics.

Patients in regimens A, B, and C undergo leukapheresis after receiving filgrastim (G-CSF) by subcutaneous (SC) injections.

* Regimen A: Patients without evidence of neuraxis dissemination receive five 21 day courses of the following chemotherapy: cisplatin IV over 6 hours on day 0; etoposide and cyclophosphamide IV over 1 hour on days 1 and 2; vincristine IV on days 0, 7, and 14 of courses 1, 2, and 3; and G-CSF SC beginning on day 3 of each course and continuing until blood counts recover or up to 48 hours before the start of the next course. Patients with evidence of neuraxis dissemination also receive high-dose methotrexate IV over 4 hours on day 3 and leucovorin calcium orally or by IV bolus starting 24 hours prior to methotrexate and continuing every 6 hours until methotrexate levels have diminished.
* Regimen B (closed to accrual effective 3/30/2000): Patients receive three 21-28 day courses of the following chemotherapy: vincristine IV on days 0, 7, and 14 of each course; carboplatin IV over 4 hours on days 3 and 4 of each course; oral procarbazine daily on days 0-4; oral lomustine on days 3 and 4; and G-CSF SC daily beginning 24 hours following the last dose of carboplatin and continuing until blood counts recover or up to 48 hours before the start of the next course. On day 7 of each course, patients also receive peripheral blood stem cell (PBSC) reinfusion following chemotherapy. Oral lomustine is administered only for the first two courses.
* Regimen C (open to accrual effective 07/21/2000): Patients receive four 28 day courses of the following chemotherapy: carboplatin IV over 4 hours on days 0 and 1 of each course; vincristine IV on days 0, 7, and 14 of the first three courses only; oral temozolomide daily on days 0-4; and G-CSF SC daily beginning on day 5 and continuing until blood counts recover.

After regimen A, B, or C and in the absence of disease progression, patients undergo consolidation myeloablative chemotherapy by receiving carboplatin IV over 4 hours on days -8, -7, and -6, and then thiotepa IV over 3 hours followed by etoposide IV on days -5, -4, and -3. Patients with malignant gliomas or unbiopsied diffuse intrinsic pontine tumors do not receive etoposide. On day 0, patients are reinfused with autologous PBSC. Following recovery from consolidation chemotherapy, patients with radiographic or cytologic evidence of residual disease undergo radiotherapy.

Patients are followed at 3 months, then every 3 months for the first 2 years, then every 6 months for years 2-4, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 96 patients (73 for regimen A and 23 for regimen C) will be accrued for this study. (Regimen B closed to accrual effective 3/30/2000.)

Conditions

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Brain and Central Nervous System Tumors Neuroblastoma Retinoblastoma Sarcoma

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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filgrastim

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

etoposide

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

methotrexate

Intervention Type DRUG

temozolomide

Intervention Type DRUG

thiotepa

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

autologous bone marrow transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Myxopapillary ependymoma of the spinal cord, low grade brainstem astrocytoma, primary CNS lymphoma or solid leukemic lesion (i.e., chloroma, granulocytic sarcoma), or primary CNS germ cell tumor

PATIENT CHARACTERISTICS:

Age:

* Under 10 at diagnosis

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin less than 1.5 mg/dL
* SGPT less than 2.5 times upper limit of normal

Renal:

* Creatinine clearance greater than 60 mL/min

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Prior corticosteroids allowed
* No concurrent corticosteroids for the sole purpose of antiemesis

Radiotherapy:

* No prior radiotherapy

Surgery:

* See Disease Characteristics
* Recovered from prior surgery
Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan L. Finlay, MB, ChB

Role: STUDY_CHAIR

NYU Langone Health

Locations

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Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status

Spectrum Health and DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status

Children's Hospital of Omaha

Omaha, Nebraska, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Beth Israel Hospital North

New York, New York, United States

Site Status

State University of New York Health Sciences Center - Stony Brook

Stony Brook, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Albert Einstein Clinical Cancer Center

The Bronx, New York, United States

Site Status

St. Vincent Mercy Medical Center

Toledo, Ohio, United States

Site Status

Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Children's Hospital

Buenos Aires, Buenos Aires, Argentina

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

Countries

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United States Argentina Canada

Other Identifiers

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NYU-P9712

Identifier Type: -

Identifier Source: secondary_id

NCI-V98-1400

Identifier Type: -

Identifier Source: secondary_id

CDR0000066174

Identifier Type: -

Identifier Source: org_study_id