High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas

NCT ID: NCT00078988

Last Updated: 2015-05-07

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

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-10-31

Study Completion Date

2006-09-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Isotretinoin may be effective in preventing recurrence of glioma. It is not yet known which regimen of chemotherapy plus autologous stem cell transplantation with or without isotretinoin is more effective in treating recurrent high-grade glioma.

PURPOSE: This randomized phase III trial is studying high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation to see how well it works compared to high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation and isotretinoin in treating young patients with recurrent high-grade glioma.

Detailed Description

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OBJECTIVES:

* Compare the event-free survival and overall survival of pediatric patients with recurrent high-grade gliomas treated with a single course of high-dose carboplatin, etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation with or without isotretinoin.
* Compare the number of hospital days and time to engraftment in patients treated with these regimens.
* Compare the toxic death rate in patients treated with these regimens.
* Compare the tolerability of isotretinoin in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade glioma).

* Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1 of 2 treatment arms.

* Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are reinfused on day 0.
* Arm II (intermediate-dose chemotherapy and ASCR): Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
* Maintenance therapy: After recovery from chemotherapy (approximately day 30 post-transplantation), all patients are further randomized to 1 of 2 maintenance arms.

* Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
* Arm II: Patients do not receive maintenance therapy. In all arms, treatment continues in the absence of disease progression.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for this study within 5 years.

Conditions

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Brain Tumor Central Nervous System Tumor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (high-dose chemotherapy and ASCR)

Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given IV

carboplatin

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

isotretinoin

Intervention Type DRUG

Given IV

thiotepa

Intervention Type DRUG

Given IV

autologous bone marrow transplantation

Intervention Type PROCEDURE

Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.

Arm II (intermediate-dose chemotherapy and ASCR)

Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given IV

carboplatin

Intervention Type DRUG

Given IV

thiotepa

Intervention Type DRUG

Given IV

autologous bone marrow transplantation

Intervention Type PROCEDURE

Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.

Arm III (isotretinoin)

Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.

Group Type EXPERIMENTAL

isotretinoin

Intervention Type DRUG

Given IV

Arm IV (no isotretinoin)

Patients do not receive maintenance therapy.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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filgrastim

Given IV

Intervention Type BIOLOGICAL

carboplatin

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

isotretinoin

Given IV

Intervention Type DRUG

thiotepa

Given IV

Intervention Type DRUG

autologous bone marrow transplantation

Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.

Intervention Type PROCEDURE

Other Intervention Names

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Granulocyte Colony-Stimulating Factor r-metHuG-CSF G-CSF Neupogen NSC 614629 Paraplain CBDCA NSC #241240 VP-16 VePesid Etopophos NSC #141540 13-cis-retinoic acid RO-43 780 Accutane NSC#329481 Tespa Thiophosphamide Triethylenethiophosphoramide Tspa WR-45312 NSC#6396 Stem Cell Reinfusion Peripheral Stem Cell Collection

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of 1 of the following high-grade gliomas:

* Glioblastoma multiforme
* Anaplastic astrocytoma
* Gliosarcoma
* Disease in first relapse
* No primary brainstem or spinal cord gliomas
* No secondary glioblastomas arising after prior treatment for a non-glial tumor
* Prior local radiotherapy of 5,000-6,000 cGy required
* Less than 1.5 cm of residual gadolinium-enhancing tumor in maximal cross-sectional diameter by MRI
* No metastatic tumor by spinal MRI

PATIENT CHARACTERISTICS:

Age

* Under 21 at diagnosis

Performance status

* Lansky 50-100% OR
* Karnofsky 50-100%

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 500/mm\^3
* Platelet count ≥ 100,000/mm\^3 (transfusion independent)

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT \< 2.5 times ULN

Renal

* Glomerular filtration rate ≥ 60 mL/min AND/OR
* Creatinine clearance ≥ 60 mL/min

Cardiovascular

* Shortening fraction ≥ 27% by echocardiogram OR
* Ejection fraction ≥ 50% by MUGA

Pulmonary

* No dyspnea at rest
* No exercise intolerance
* Pulse oximetry \> 94%

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* More than 4 weeks since prior chemotherapy
* No prior thiotepa
* No prior myeloablative chemotherapy

Endocrine therapy

* No concurrent corticosteroids

Radiotherapy

* See Disease Characteristics
* More than 8 weeks since prior radiotherapy
* No prior craniospinal radiotherapy

Surgery

* Not specified
Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ziad Khatib, MD

Role: STUDY_CHAIR

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Sharon L. Gardner, MD

Role: STUDY_CHAIR

NYU Langone Health

Locations

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Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Children's Hospital and Research Center - Oakland

Oakland, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

Children's Hospital and Health Center - San Diego

San Diego, California, United States

Site Status

Children's Hospital Cancer Center

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, United States

Site Status

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Spectrum Health Cancer Care - Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Children's Hospital of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Fairview University Medical Center - University Campus

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Columbus Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Sioux Valley Hospital and University of South Dakota Medical Center

Sioux Falls, South Dakota, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

INOVA Fairfax Hospital

Fairfax, Virginia, United States

Site Status

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Site Status

Massey Cancer Center at Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, Canada

Site Status

Countries

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United States Australia Canada

Other Identifiers

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COG-ACNS0231

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000353207

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02578

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACNS0231

Identifier Type: -

Identifier Source: org_study_id

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