Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System
Status: | Active, not recruiting |
---|---|
Conditions: | Brain Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | Any - 21 |
Updated: | 2/7/2019 |
Start Date: | December 8, 2008 |
Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
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.
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.
PRIMARY OBJECTIVES:
I. To determine the 6-, 12-, and 24-month event-free survival and overall survival of
children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT),
diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical
analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell
rescue, and radiation therapy.
II. To compare the outcome of very young patients (under 3 years old) on this study whose
histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and
CCG-9921.
SECONDARY OBJECTIVES:
I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in
combination with radiation therapy.
II. To contribute tumor samples from which biologic and gene expression data can be developed
to yield prognostic indicators and provide direction for future treatment strategies.
III. To develop a clinical and biologic database on which future studies can be based.
OUTLINE:
INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15
and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of
methotrexate, patients receive leucovorin calcium orally (PO) or IV every 6 hours until the
serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour
on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4
and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive
filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing
until ANC recovers. When ANC is > 1,000/uL post nadir, patients receive G-CSF twice daily for
stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are
harvested once daily, as needed, after each course of induction therapy until a total of 6 x
10^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses.
After completion of induction therapy, patients are re-evaluated. Patients with progressive
disease are removed from study. Patients with radiographic evidence of residual tumor are
encouraged to undergo second-look surgery prior to proceeding to radiotherapy or
consolidation therapy; patients with complete response, partial response, or stable disease
are assigned to 1 of 2 arm.
ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less
than 12 months, supratentorial site with M0 involvement or patients with disseminated disease
of any primary site or age):
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction
therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over
4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous
peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF
IV or SC once daily beginning 24 hours after stem cell infusion and continuing 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.
RADIATION THERAPY: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the
brain (and the spine if needed) 5 days a week for 5-6 weeks.
ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement
or patients greater than or equal to 12 months, supratentorial site with M0 involvement):
Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy,
patients receive consolidation therapy and stem cell rescue as in Arm I
NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the
prior clearance of methotrexate to a level of < 0.1 micromoles.
After completion of study treatment, patients are followed periodically for up to 10 years.
I. To determine the 6-, 12-, and 24-month event-free survival and overall survival of
children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT),
diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical
analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell
rescue, and radiation therapy.
II. To compare the outcome of very young patients (under 3 years old) on this study whose
histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and
CCG-9921.
SECONDARY OBJECTIVES:
I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in
combination with radiation therapy.
II. To contribute tumor samples from which biologic and gene expression data can be developed
to yield prognostic indicators and provide direction for future treatment strategies.
III. To develop a clinical and biologic database on which future studies can be based.
OUTLINE:
INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15
and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of
methotrexate, patients receive leucovorin calcium orally (PO) or IV every 6 hours until the
serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour
on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4
and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive
filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing
until ANC recovers. When ANC is > 1,000/uL post nadir, patients receive G-CSF twice daily for
stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are
harvested once daily, as needed, after each course of induction therapy until a total of 6 x
10^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses.
After completion of induction therapy, patients are re-evaluated. Patients with progressive
disease are removed from study. Patients with radiographic evidence of residual tumor are
encouraged to undergo second-look surgery prior to proceeding to radiotherapy or
consolidation therapy; patients with complete response, partial response, or stable disease
are assigned to 1 of 2 arm.
ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less
than 12 months, supratentorial site with M0 involvement or patients with disseminated disease
of any primary site or age):
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction
therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over
4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous
peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF
IV or SC once daily beginning 24 hours after stem cell infusion and continuing 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.
RADIATION THERAPY: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the
brain (and the spine if needed) 5 days a week for 5-6 weeks.
ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement
or patients greater than or equal to 12 months, supratentorial site with M0 involvement):
Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy,
patients receive consolidation therapy and stem cell rescue as in Arm I
NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the
prior clearance of methotrexate to a level of < 0.1 micromoles.
After completion of study treatment, patients are followed periodically for up to 10 years.
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
We found this trial at
88
sites
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1201 Camino de Salud Northeast
Albuquerque, New Mexico 87131
Albuquerque, New Mexico 87131
(505) 272-4946
University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
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Children's Hospital of Alabama Children
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Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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Rainbow Babies and Children's Hospital UH Rainbow Babies & Children’s Hospital is a 244-bed, full-service...
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Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
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Driscoll Children's Hospital Driscoll Children's Hospital was built because Clara Driscoll's will requested that a...
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Lee Memorial Health System Our origins can be traced to the Fall of 1916 when...
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Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
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University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
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Children's Mercy Hospital Children's Mercy Hospitals and Clinics continues redefining pediatric medicine throughout the Midwest...
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529 West Markham Street
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
(501) 686-7000
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
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Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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747 52nd St
Oakland, California 94609
Oakland, California 94609
(510) 428-3000
Children's Hospital and Research Center Oakland For nearly 100 years, Children's Hospital & Research Center...
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Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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1717 South Orange Avenue # 100
Orlando, Florida 32806
Orlando, Florida 32806
(407) 650-7000
Nemours Children's Clinic - Orlando Located near downtown Orlando, Nemours Children’s Clinic, Orlando is a...
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Nemours Children's Clinic - Pensacola Nemours Children’s Clinic, Pensacola serves children and families in northwest...
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Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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Rhode Island Hospital Founded in 1863, Rhode Island Hospital in Providence, RI, is a private,...
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University of Rochester The University of Rochester is one of the country's top-tier research universities....
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7700 Floyd Curl Dr
San Antonio, Texas 78229
San Antonio, Texas 78229
(210) 575-7000
Methodist Children's Hospital of South Texas Methodist Children
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4502 Medical Drive
San Antonio, Texas 78284
San Antonio, Texas 78284
(210) 567-7000
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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Rady Children's Hospital - San Diego Rady Children's Hospital-San Diego is the region’s pediatric medical...
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New York Medical College The College was founded in 1860 by a group of New...
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Alfred I. duPont Hospital for Children Nemours began more than 70 years ago with the...
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401 North Broadway
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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8901 Rockville Pike
Bethesda, Maryland 20889
Bethesda, Maryland 20889
(301) 295-4000
Walter Reed National Military Medical Center The Walter Reed National Military Medical Center is one...
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Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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3110 MacCorkle Avenue Southeast
Charleston, West Virginia 25304
Charleston, West Virginia 25304
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5841 S Maryland Ave
Chicago, Illinois 60637
Chicago, Illinois 60637
1-773-702-6180
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
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Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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Palmetto Health Richland Palmetto Health Richland, originally founded in 1892 as Columbia Hospital, has a...
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4160 John R St #2122
Detroit, Michigan 48201
Detroit, Michigan 48201
(313) 833-1785
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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Cook Children's Medical Center Cook Children's Health Care System is a not-for-profit, nationally recognized pediatric...
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1600 Southwest Archer Road
Gainesville, Florida 32610
Gainesville, Florida 32610
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900 West Faris Rd.
Greenville, South Carolina 29605
Greenville, South Carolina 29605
(864)455-8898
BI-LO Charities Children's Cancer Center The BI-LO Charities Children
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Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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Riley Hospital for Children Riley Hospital for Children at IU Health is a place of...
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East Tennessee Children's Hospital East Tennessee Children's Hospital is a not-for-profit, private, independent pediatric medical...
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Loyola University Medical Center Loyola University Health System is committed to excellence in patient care...
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9000 W Wisconsin Ave #270
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
(414) 266-2000
Children's Hospital of Wisconsin Nothing matters more than our children. At Children's Hospital of Wisconsin,...
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2525 Chicago Ave
Minneapolis, Minnesota 55404
Minneapolis, Minnesota 55404
(612) 813-6000
Children's Hospitals and Clinics of Minnesota - Minneapolis Children's Hospitals and Clinics of Minnesota is...
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1430 Tulane Ave Suite SL32
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
(504) 588-5912
Tulane University Health Sciences Center One of the nation's most recognized centers for medical education,...
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Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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940 NE 13th St
Oklahoma City, Oklahoma 73190
Oklahoma City, Oklahoma 73190
(405) 271-6458
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
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Children's Hospital and Medical Center of Omaha Children's Hospital & Medical Center has a rich...
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Saint Joseph's Regional Medical Center Rich in history, St. Joseph's Healthcare System has evolved from...
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660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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Overlook Hospital Atlantic Health System
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Mercy Children's Hospital Mercy Children's Hospital is a regional resource for advanced pediatric care located...
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111 Michigan Ave NW
Washington, District of Columbia
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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Saint Mary's Hospital Our team of dedicated physicians, nurses and staff offer a broad spectrum...
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