Phase III Randomized Study Of Chimeric Antibody 14.18 (CH14.18) In High Risk Neuroblastoma Following Myeloablative Therapy And Autologous Stem Cell Rescue
PRIMARY OBJECTIVES:
I. Determine if monoclonal antibody Chl4.18 + cytokines + isotretinoin (13-cis-retinoic
acid, or RA) improves event free survival after myeloablative therapy and stem cell rescue
as compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-ASCT
response of CR, VGPR, or PR.
SECONDARY OBJECTIVES:
I. Determine if monoclonal antibody Chl4.18 + cytokines + isotretinoin (13-cis-retinoic
acid, or RA) improves overall survival after myeloablative therapy and stem cell rescue as
compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-ASCT
response of CR, VGPR, or PR.
II. Determine if immunotherapy + RA improves event free survival and overall survival as
compared to RA alone, in the subgroup of high risk INSS Stage 4 neuroblastoma patients who
have achieved a pre-ASCT response of CR, VGPR, or PR.
III. In the subgroup of neuroblastoma patients who have achieved a pre-ASCT response of CR,
VGPR, or PR, determine if there is a difference between the two randomized regimens in
reducing the minimal residual disease (MRD) burden as detected by the following parameters:
meta-iodobenylguanidine (MIBG) scan, immunocytology (IC) of blood and bone marrow samples,
RT-PCR for tyrosine hydroxylase, PGP 9.5, and MAGE-1 in blood and bone marrow.
IV. Determine if change from baseline of MRD as measured by above parameters is associated
with event free and overall survival V. Determine whether tumor biology at diagnosis
correlates with event-free and overall survival, for either of the randomized regimens.
VI. Determine the toxicities of the combination of monoclonal antibody Ch14.18 with
cytokines.
VII. To explore the relationship between antibody-dependent cellular cytoxicity (ADCC) and
EFS.
VIII. To determine a descriptive profile of human anti-chimeric antibody (HACA) during
immunotherapy.
IX. To compare the outcome data of the patients with persistent disease documented by biopsy
(Stratum 07) to the historical data for the analogous patients from CCG-3981.
X. To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to
pharmacogenomic parameters and determine if these levels and/or genetic variations correlate
with EFS or systemic toxicity.
XI. To further describe and refine the EFS and OS estimates and baseline characteristics for
subjects receiving Chl4.18 + cytokines + RA, following cessation of the randomized portion
of the study.
XII. To further describe the safety and toxicity of Chl4.18 + cytokines + RA under the new
administration guidelines implemented following cessation of the randomized portion of the
study with focus on: a) number of courses delivered per subject; b) number of dose
reductions or stoppage (ch14.18 and/or IL-2); and c) number of toxic deaths.
XIII. To determine the potential effect of ch14.18 on cardiac repolarization and to evaluate
ch14.18 plasma levels.
XIV. To determine if the presence of naturally occurring anti-glycan antibodies correlates
with allergic reactions and blood levels of ch14.18.
XV. To determine if the genotype of FcR and Kir/Kir-Ligand correlate with EFS.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
pre-autologous stem cell transplantation (ASCT) response (complete vs very good partial vs
partial), stem cells received (purged vs unpurged), and frontline chemotherapy (COG-A3973 vs
POG 9341/9342 vs COG-ANGL02P1 vs other therapy). A further stratum consists of patients with
biopsy-confirmed post-ASCT persistent disease who are also enrolled on COG-A3973 or
COG-ANBL0532. These patients are not randomized but assigned to treatment arm II. Patients
in the first set of strata are randomized to 1 of 2 treatment arms.
ARM I: Beginning on day 67 post-ASCT, patients receive oral isotretinoin twice daily for 14
days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or
unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced
disease progression and have not received any further anti-neuroblastoma therapy following
completion of isotretinoin therapy.
ARM II: Beginning on day 56 post-ASCT, patients receive immunotherapy comprising
sargramostim (GM-CSF) subcutaneously (SC) or IV over 2 hours on days 0-13 during courses 1,
3, and 5 and monoclonal antibody Ch14.18 IV over 10-20 hours on days 3-6 of courses 1-5.
Patients also receive interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2
and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease
progression or unacceptable toxicity. Patients also receive oral isotretinoin as in arm I
beginning on and day 11 of immunotherapy.
Patients are followed periodically for 10 years.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival (EFS)
An event is defined as a relapse, progressive disease, secondary malignancy, or death
Time from study enrollment until the first occurrence of an event or until last contact with the patient if no event occurs, assessed up to 3 years
No
Alice Yu
Principal Investigator
Children's Oncology Group
United States: Food and Drug Administration
NCI-2009-01064
NCT00026312
October 2001
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Johns Hopkins University | Baltimore, Maryland 21205 |
Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Mayo Clinic | Rochester, Minnesota 55905 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
Hurley Medical Center | Flint, Michigan 48503 |
Rhode Island Hospital | Providence, Rhode Island 02903 |
Medical City Dallas Hospital | Dallas, Texas 75230 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
Sinai Hospital of Baltimore | Baltimore, Maryland 21225 |
Geisinger Medical Center | Danville, Pennsylvania 17822-0001 |
Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
Morristown Memorial Hospital | Morristown, New Jersey 07962-1956 |
Marshfield Clinic | Marshfield, Wisconsin 54449 |
Loma Linda University Medical Center | Loma Linda, California 92354 |
Baptist Hospital of Miami | Miami, Florida 33176-2197 |
Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
New York Medical College | Valhalla, New York 10595 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Broward General Medical Center | Fort Lauderdale, Florida 33316 |
Miami Children's Hospital | Miami, Florida 33155-4069 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Advocate Hope Children's Hospital | Oak Lawn, Illinois 60453 |
Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
Maine Children's Cancer Program | Scarborough, Maine 04074-9308 |
Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
Legacy Emanuel Hospital and Health Center | Portland, Oregon 97227 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
Southern California Permanente Medical Group | Downey, California 90242 |
Children's Hospital Central California | Madera, California 93638-8762 |
Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
Winthrop University Hospital | Mineola, New York 11501 |
Mount Sinai Medical Center | New York, New York 10029 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
Naval Medical Center - Portsmouth | Portsmouth, Virginia 23708-2197 |
Montefiore Medical Center | Bronx, New York 10467-2490 |
Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
Dell Children's Medical Center of Central Texas | Austin, Texas 78723 |
Children's Hospital and Research Center at Oakland | Oakland, California 94609-1809 |
City of Hope Medical Center | Duarte, California 91010 |
Lehigh Valley Hospital - Muhlenberg | Bethlehem, Pennsylvania 18017 |
Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
Lee Memorial Health System | Fort Myers, Florida 33902 |
University of Virginia | Charlottesville, Virginia 22908 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
Children's Hospital of Alabama | Birmingham, Alabama 35233 |
Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
Vanderbilt University | Nashville, Tennessee 37232-6305 |
University of North Carolina | Chapel Hill, North Carolina 27599 |
Duke University Medical Center | Durham, North Carolina 27710 |
University of Florida | Gainesville, Florida 32610-0277 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids, Michigan 49503 |
Yale University | New Haven, Connecticut 06520 |
Wayne State University | Detroit, Michigan 48202 |
Legacy Emanuel Children's Hospital | Portland, Oregon 97227 |
BI-LO Charities Children's Cancer Center | Greenville, South Carolina 29605 |
University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
Dartmouth Hitchcock Medical Center | Lebanon, New Hampshire 03756 |
University Of Vermont | Burlington,, Vermont 05403 |
Albany Medical Center | Albany, New York 12208 |
University of Texas Southwestern Medical Center | Dallas, Texas |
University of Kentucky | Lexington, Kentucky 40536-0098 |
UC Davis Comprehensive Cancer Center | Sacramento, California 95817 |
Oregon Health and Science University | Portland, Oregon 97201 |
Virginia Commonwealth University | Richmond, Virginia |
Florida Hospital | Orlando, Florida 32803 |
Memorial Health University Medical Center | Savannah, Georgia 31404 |
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
Seattle Children's Hospital | Seattle, Washington 98105 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
Childrens Memorial Hospital | Chicago, Illinois 60614 |
Kaiser Permanente-Oakland | Oakland, California 94611 |
M D Anderson Cancer Center- Orlando | Orlando, Florida 32806 |
Saint Vincent Hospital and Health Services | Indianapolis, Indiana 46260 |
Saint John Hospital and Medical Center | Detroit, Michigan 48236 |
Michigan State University - Breslin Cancer Center | East Lansing, Michigan 48824-1313 |
Saint John's Mercy Medical Center | Saint Louis, Missouri 63141 |
Nevada Cancer Research Foundation CCOP | Las Vegas, Nevada 89106 |
Columbia University Medical Center | New York, New York 10032 |
State University of New York Upstate Medical University | Syracuse, New York 13210 |
Mission Hospitals Inc | Asheville, North Carolina 28801 |
Saint Vincent Hospital | Green Bay, Wisconsin 54301 |
University of Maryland Greenebaum Cancer Center | Baltimore, Maryland 21201 |
University of Illinois | Chicago, Illinois 60612 |
Cook Children's Medical Center | Fort Worth, Texas 76104 |
Memorial Healthcare System - Joe DiMaggio Children's Hospital | Hollywood, Florida 33021 |
The Children's Medical Center of Dayton | Dayton, Ohio 45404 |
University of Minnesota Medical Center-Fairview | Minneapolis, Minnesota 55455 |
Children's Oncology Group | Arcadia, California 91006-3776 |
C S Mott Children's Hospital | Ann Arbor, Michigan 48109 |
Southern Illinois University | Springfield, Illinois 62702 |
University Of Missouri-Columbia | Columbia, Missouri 65212 |
Walter Reed National Military Medical Center | Bethesda, Maryland 20889 |
Riley Hospital for Children | Indianapolis, Indiana 46202 |
Cardinal Glennon Children's Medical Center | St. Louis, Missouri 63104 |
UMDNJ - Robert Wood Johnson University Hospital | New Brunswick, New Jersey 08903 |
Phoenix Childrens Hospital | Phoenix, Arizona 85016 |
Childrens Hospital of Orange County | Orange, California 92868-3874 |
Alfred I duPont Hospital for Children | Wilmington, Delaware 19803 |
Nemours Children's Clinic - Jacksonville | Jacksonville, Florida 32207-8426 |
Nemours Childrens Clinic - Orlando | Orlando, Florida 32806 |
Saint Joseph Children's Hospital of Tampa | Tampa, Florida 33607 |
Children's Healthcare of Atlanta - Egleston | Atlanta, Georgia 30322 |
The Childrens Mercy Hospital | Kansas City, Missouri 64108 |
Rainbow Babies and Childrens Hospital | Cleveland, Ohio 44106 |
Penn State Hershey Children's Hospital | Hershey, Pennsylvania 17033 |
Palmetto Health Richland | Columbia, South Carolina 29203 |
East Tennessee Childrens Hospital | Knoxville, Tennessee 37916 |
Children's Hospital and Medical Center of Omaha | Omaha, Nebraska 68114 |
Childrens Hospital-King's Daughters | Norfolk, Virginia 23507 |
Sanford Medical Center-Fargo | Fargo, North Dakota 58122 |
Children's Hospital Colorado | Aurora, Colorado 80045 |
Lucile Packard Children's Hospital Stanford University | Palo Alto, California 94304 |
University of California San Francisco Medical Center-Parnassus | San Francisco, California 94143 |
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver, Colorado 80218 |
Raymond Blank Children's Hospital | Des Moines, Iowa 50309 |
Children's Hospital-Main Campus | New Orleans, Louisiana 70118 |
The Toledo Hospital/Toledo Children's Hospital | Toledo, Ohio 43606 |
Saint Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134 |
Greenville Cancer Treatment Center | Greenville, South Carolina 29605 |
Sanford USD Medical Center - Sioux Falls | Sioux Falls, South Dakota 57117-5134 |
T C Thompson Children's Hospital | Chattanooga, Tennessee 37403 |
Carilion Clinic Children's Hospital | Roanoke, Virginia 24014 |
Providence Sacred Heart Medical Center and Children's Hospital | Spokane, Washington 99204 |