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

Last updated: May 6, 2015
Sponsor: Children's Oncology Group
Overall Status: Completed

Phase

3

Condition

Brain Tumor

Gliomas

Memory Loss

Treatment

N/A

Clinical Study ID

NCT00078988
ACNS0231
COG-ACNS0231
CDR0000353207
NCI-2012-02578
U10CA098543
  • Ages < 20
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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

Study Design

Total Participants: 1
Study Start date:
October 01, 2004
Estimated Completion Date:
September 30, 2006

Study Description

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.

Connect with a study center

  • Princess Margaret Hospital for Children

    Perth, Western Australia 6001
    Australia

    Site Not Available

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia V6H 3V4
    Canada

    Site Not Available

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario L8N 3Z5
    Canada

    Site Not Available

  • Hospital for Sick Children

    Toronto, Ontario M5G 1X8
    Canada

    Site Not Available

  • Hopital Sainte Justine

    Montreal, Quebec H3T 1C5
    Canada

    Site Not Available

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec H3H 1P3
    Canada

    Site Not Available

  • Centre Hospitalier Universitaire de Quebec

    Ste-Foy, Quebec G1V 4G2
    Canada

    Site Not Available

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas 72205
    United States

    Site Not Available

  • Children's Hospital and Research Center - Oakland

    Oakland, California 94609-1809
    United States

    Site Not Available

  • University of California Davis Cancer Center

    Sacramento, California 95817
    United States

    Site Not Available

  • Children's Hospital and Health Center - San Diego

    San Diego, California 92123-4282
    United States

    Site Not Available

  • Children's Hospital Cancer Center

    Denver, Colorado 80218-1088
    United States

    Site Not Available

  • Children's National Medical Center

    Washington, District of Columbia 20010-2970
    United States

    Site Not Available

  • University of Florida Shands Cancer Center

    Gainesville, Florida 32610-0232
    United States

    Site Not Available

  • Nemours Children's Clinic

    Jacksonville, Florida 32207
    United States

    Site Not Available

  • Miami Children's Hospital

    Miami, Florida 33155
    United States

    Site Not Available

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida 33136
    United States

    Site Not Available

  • All Children's Hospital

    St. Petersburg, Florida 33701
    United States

    Site Not Available

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

    Tampa, Florida 33607
    United States

    Site Not Available

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida 33407
    United States

    Site Not Available

  • Emory University Hospital - Atlanta

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii 95813
    United States

    Site Not Available

  • Indiana University Cancer Center

    Indianapolis, Indiana 46202-5289
    United States

    Site Not Available

  • St. Vincent Indianapolis Hospital

    Indianapolis, Indiana 46260
    United States

    Site Not Available

  • Kosair Children's Hospital

    Louisville, Kentucky 40232
    United States

    Site Not Available

  • CancerCare of Maine at Eastern Maine Medial Center

    Bangor, Maine 04401
    United States

    Site Not Available

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts 02111
    United States

    Site Not Available

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan 48201-1379
    United States

    Site Not Available

  • Spectrum Health Cancer Care - Butterworth Campus

    Grand Rapids, Michigan 49503-2560
    United States

    Site Not Available

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

    Grosse Pointe Woods, Michigan 48236
    United States

    Site Not Available

  • Children's Hospital of Minnesota - Minneapolis

    Minneapolis, Minnesota 55404
    United States

    Site Not Available

  • Fairview University Medical Center - University Campus

    Minneapolis, Minnesota 55455
    United States

    Site Not Available

  • University of Mississippi Medical Center

    Jackson, Mississippi 39216-4505
    United States

    Site Not Available

  • Children's Mercy Hospital

    Kansas City, Missouri 64108
    United States

    Site Not Available

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St. Louis, Missouri 63110
    United States

    Site Not Available

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

    New Brunswick, New Jersey 08903
    United States

    Site Not Available

  • Roswell Park Cancer Institute

    Buffalo, New York 14263-0001
    United States

    Site Not Available

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York 10032
    United States

    Site Not Available

  • NYU Cancer Institute at New York University Medical Center

    New York, New York 10016
    United States

    Site Not Available

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

    Rochester, New York 14642
    United States

    Site Not Available

  • SUNY Upstate Medical University Hospital

    Syracuse, New York 13210
    United States

    Site Not Available

  • New York Medical College

    Valhalla, New York 10595
    United States

    Site Not Available

  • Children's Hospital Medical Center of Akron

    Akron, Ohio 44308-1062
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229-3039
    United States

    Site Not Available

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio 44106-5000
    United States

    Site Not Available

  • Columbus Children's Hospital

    Columbus, Ohio 43205-2696
    United States

    Site Not Available

  • Children's Medical Center - Dayton

    Dayton, Ohio 45404-1815
    United States

    Site Not Available

  • Oklahoma University Medical Center

    Oklahoma City, Oklahoma 73104
    United States

    Site Not Available

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania 17033-0850
    United States

    Site Not Available

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Sioux Valley Hospital and University of South Dakota Medical Center

    Sioux Falls, South Dakota 57117-5039
    United States

    Site Not Available

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas 76104-9958
    United States

    Site Not Available

  • Covenant Children's Hospital

    Lubbock, Texas 79410
    United States

    Site Not Available

  • Primary Children's Medical Center

    Salt Lake City, Utah 84113-1100
    United States

    Site Not Available

  • INOVA Fairfax Hospital

    Fairfax, Virginia 22031
    United States

    Site Not Available

  • Children's Hospital of the King's Daughters

    Norfolk, Virginia 23507-1971
    United States

    Site Not Available

  • Massey Cancer Center at Virginia Commonwealth University

    Richmond, Virginia 23298-0037
    United States

    Site Not Available

  • University of Wisconsin Comprehensive Cancer Center

    Madison, Wisconsin 53792-6164
    United States

    Site Not Available

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin 54449
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.