Purpose

This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.

Category

IRB Number
20090391HU
NCT Number
NCT00653068
Open to Enrollment
Yes
Sponsor
Children's Oncology Group -



Study Contact

Principal Investigator
Anne-Marie Langevin

Regulatory Point of Contact
Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu



Eligibility

Eligible Ages
Under21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    • Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)

      • Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible
      • Patients with MRI evidence of spinal disease are eligible
    • Must have undergone definitive surgery in the past 31 days
    • Cranial MRI (with and without gadolinium) must be done pre-operatively

      • Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery
    • Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium)
    • Life expectancy > 8 weeks
    • ANC > 1,000/uL
    • Platelet count > 100,000/uL (transfusion independent)
    • Hemoglobin > 8 g/dL (RBC transfusions allowed)
    • Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR >= 60 mL/min
    • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
    • AST and ALT < 2 times ULN for age
    • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 47% by radionuclide angiogram
    • No evidence of dyspnea at rest
    • Pulse oximetry > 94% on room air
    • Not pregnant or nursing
    • Negative pregnancy test
    • Fertile patients must use effective contraception
    • No prior radiotherapy or chemotherapy except for the following:

      • Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged)
      • Prior corticosteroids allowed

Exclusion Criteria

    >

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Childhood Atypical Teratoid/Rhabdoid Tumor
  • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Arm I (chemotherapy, autologous PBSC, 3D-CRT)

    Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
  • Drug: Cisplatin

    Given IV

    Other names:

    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum

  • Drug: Etoposide

    Given IV

    Other names:

    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213

  • Other: Laboratory Biomarker Analysis

    Correlative studies

  • Drug: Methotrexate

    Given IV

    Other names:

    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS

  • Drug: Vincristine Sulfate

    Given IV

    Other names:

    • Kyocristine
    • Leurocristine sulfate
    • Leurocristine, sulfate
    • Oncovin
    • Vincasar
    • Vincosid
    • Vincrex
    • Vincristine, sulfate

  • Procedure: Autologous Hematopoietic Stem Cell Transplantation

    Undergo autologous PBSC rescue

    Other names:

    • Autologous Hematopoietic Cell Transplantation
    • autologous stem cell transplantation

  • Radiation: 3-Dimensional Conformal Radiation Therapy

    Undergo 3D-CRT

    Other names:

    • 3-dimensional radiation therapy
    • 3D CONFORMAL RADIATION THERAPY
    • 3D CRT
    • 3D-CRT
    • Conformal Therapy
    • Radiation Conformal Therapy

  • Drug: Carboplatin

    Given IV

    Other names:

    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Para

  • Drug: Cyclophosphamide

    Given IV

    Other names:

    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen <

  • Biological: Filgrastim

    Given IV or SC

    Other names:

    • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
    • G-CSF
    • Neupogen
    • r-metHuG-CSF
    • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
    • rG-CSF
    • Tevagrastim

  • Drug: Leucovorin Calcium

    Given IV or PO

    Other names:

    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • citrovorum factor
    • C

  • Drug: Thiotepa

    Given IV

    Other names:

    • 1,1',1''-Phosphinothioylidynetrisaziridine
    • Girostan
    • N,N', N''-Triethylenethiophosphoramide
    • Oncotiotepa
    • STEPA
    • Tepadina
    • TESPA
    • Tespamin
    • Tespamine
    • Thio-Tep

  • Experimental

    Arm II (chemotherapy, 3D-CRT, autologous PBSC)

    Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Drug: Cisplatin

    Given IV

    Other names:

    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum

  • Drug: Etoposide

    Given IV

    Other names:

    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213

  • Other: Laboratory Biomarker Analysis

    Correlative studies

  • Drug: Methotrexate

    Given IV

    Other names:

    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS

  • Drug: Vincristine Sulfate

    Given IV

    Other names:

    • Kyocristine
    • Leurocristine sulfate
    • Leurocristine, sulfate
    • Oncovin
    • Vincasar
    • Vincosid
    • Vincrex
    • Vincristine, sulfate

  • Procedure: Autologous Hematopoietic Stem Cell Transplantation

    Undergo autologous PBSC rescue

    Other names:

    • Autologous Hematopoietic Cell Transplantation
    • autologous stem cell transplantation

  • Radiation: 3-Dimensional Conformal Radiation Therapy

    Undergo 3D-CRT

    Other names:

    • 3-dimensional radiation therapy
    • 3D CONFORMAL RADIATION THERAPY
    • 3D CRT
    • 3D-CRT
    • Conformal Therapy
    • Radiation Conformal Therapy

  • Drug: Carboplatin

    Given IV

    Other names:

    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Para

  • Drug: Cyclophosphamide

    Given IV

    Other names:

    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen <

  • Biological: Filgrastim

    Given IV or SC

    Other names:

    • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
    • G-CSF
    • Neupogen
    • r-metHuG-CSF
    • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
    • rG-CSF
    • Tevagrastim

  • Drug: Leucovorin Calcium

    Given IV or PO

    Other names:

    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • citrovorum factor
    • C

  • Drug: Thiotepa

    Given IV

    Other names:

    • 1,1',1''-Phosphinothioylidynetrisaziridine
    • Girostan
    • N,N', N''-Triethylenethiophosphoramide
    • Oncotiotepa
    • STEPA
    • Tepadina
    • TESPA
    • Tespamin
    • Tespamine
    • Thio-Tep