Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma

Condition(s) targeted: Neuroblastoma

Intervention: therapeutic immune globulin (Drug); observation (Procedure)

Phase: Phase 3

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Pedro A. de Alarcon, MD, Study Chair, Affiliation: Saint Jude Midwest Affiliate

RATIONALE: Drugs used in chemotherapy, work in different ways to stop tumor cells from dividing so they stop growing or die. Steroid therapy decreases inflammation. Combining chemotherapy and steroid therapy with immunoglobulin may be effective in treating abnormal muscle movement associated with neuroblastoma.

PURPOSE: This randomized phase II trial is studying cyclophosphamide, prednisone, and immunoglobulin to see how well they work compared to cyclophsophamide and prednisone alone in treating patients with abnormal trunk muscle movements associated with neuroblastoma.

Official title: A Phase III Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone

Study design: Treatment, Randomized, Active Control

Primary outcome:

Efficacy as measured by assessment of response of opsoclonus, gait, neural, stance, arm and hand function at baseline, 2 months, 6 months, and 1 year

Response as measured by assessment of opsoclonus, gait, neural, stance, arm and hand function at baseline, 2 months, 6 months, and 1 year

Secondary outcome:

Motor coordination as assessed by neurological examination and Vineland Adaptive Behavior Scale at baseline, 1 and 5 years

Functional outcome as assessed by age-appropriate neuropsychological testing at baseline, 1 and 5 years

Biology of neuroblastoma associated opsoclonus-myoclonus-ataxia syndrome, specifically by MRI findings, anti-neuronal antibodies, SCF findings and tumor biology at baseline, 6 months, and 1 year

Long-term prognosis for neurologic recovery by neurological examination at baseline, 1 and 5 years

Tumor outcome in terms of event-free survival and overall survival at 1, 5, and 10 years

Detailed description: OBJECTIVES:

- Determine whether cyclophosphamide and prednisone with or without immune globulin is a

reasonable baseline standard therapy for pediatric patients with neuroblastoma-associated opsoclonus-myoclonus-ataxia (OMA) syndrome.

- Determine whether immunosuppressive therapy with cyclophosphamide and prednisone is an

effective backbone therapy for OMA upon which to build additional treatment for these patients.

- Determine whether these regimens improve OMA syndrome in these patients.

- Determine whether these regimens improve motor coordination in these patients.

- Determine whether these regimens improve functional outcome in these patients.

- Compare the event-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk group per protocol COG-ANBL00B1 (low risk vs intermediate risk on COG-A3961 vs high risk on COG-A3973).

- Chemotherapy: Patients with intermediate-risk or high-risk neuroblastoma receive

chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning on day 0.

Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

All patients receive prednisone twice daily for 3 months and then every other day for 7-15 months.

- Immune globulin therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive immune globulin IV on days -2 and -1, at weeks 4, 8, 12,

16, 20, and 24, and then at months 8, 10, and 12 after therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with no response after 6 months go off treatment.

- Arm II: Patients do not receive immune globulin. Patients with unresponsive

opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.

Patients are followed during therapy every month for 6 months, at 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-52 patients (9-26 per treatment arm) will be accrued for this study within 2-5. 8 years.

Minimum age: N/A. Maximum age: 8 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Newly diagnosed neuroblastoma with tumor-associated opsoclonus-myoclonus-ataxia

syndrome

- Must enroll on study within 4 weeks of diagnosis

- Presence of opsoclonus, myoclonus, and/or ataxia associated with neuroblastoma

considered eligible

- Currently enrolled on COG neuroblastoma protocols: COG-ANBL00B1 or its successor

PATIENT CHARACTERISTICS:

Age:

- 8 and under

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Not specified

Renal:

- Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior chemotherapy

- Concurrent chemotherapy allowed

Endocrine therapy:

- No prior prednisone or corticotropin

Radiotherapy:

- Not specified

Surgery:

- Concurrent surgery allowed

Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson, Arizona 85724-5024, United States; Recruiting
Clinical Trials Office - Arizona Cancer Center at University o, Phone: 520-626-9008

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States; Recruiting
Jessica L. Boklan, Phone: 602-546-0920

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States; Recruiting
Clinical Trial Office - Arkansas Cancer Research Center at Uni, Phone: 501-686-8274

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada; Recruiting
Mason Bond, Phone: 604-875-2322

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States; Recruiting
Vincent Kiley, Phone: 916-973-7331

Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States; Recruiting
Clinical Trials Office - Loma Linda University Cancer Institut, Phone: 909-558-3375

Rady Children's Hospital - San Diego, San Diego, California 92123-4282, United States; Recruiting
Clinical Trials Office - Rady Children's Hospital - San Diego, Phone: 858-966-5934

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Children's Hospital Center for Cancer and Blood Disorders, Aurora, Colorado 80045, United States; Recruiting
Kelly Maloney, Phone: 720-777-6673

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States; Recruiting
Clinical Trials Office - Alfred I. duPont Hospital for Childre, Phone: 302-651-5755

All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting
Jerry Barbosa, Phone: 727-767-4176

Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States; Recruiting
Narayana Gowda, Phone: 561-844-6363

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States; Recruiting
Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt, Phone: 877-680-0008

Nemours Children's Clinic, Jacksonville, Florida 32207, United States; Recruiting
Eric Sandler, Phone: 904-390-3793

Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States; Recruiting
Clinical Trials Office - Sacred Heart Cancer Center, Phone: 850-416-4611

St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States; Recruiting
Clinical Trials Office - St. Joseph's Cancer Institute, Phone: 800-882-4123

University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States; Recruiting
University of Miami Sylvester Comprehensive Cancer Center Clin, Phone: 866-574-5124, Email: Sylvester@emergingmed.com

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States; Recruiting
Howard M. Katzenstein, Phone: 404-785-0853

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States; Recruiting
David O. Walterhouse, Phone: 773-755-6514

University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States; Recruiting
Clinical Trials Office - University of Chicago Cancer Research, Phone: 773-834-7424

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States; Recruiting
Clinical Trials Office - Indiana University Cancer Center, Phone: 317-274-2552

Kosair Children's Hospital, Louisville, Kentucky 40232, United States; Recruiting
Clinical Trials Office - Kosair Children's Hospital, Phone: 502-629-5500, Email: CancerResource@nortonhealthcare.org

Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States; Recruiting
Clinical Trials Office - Markey Cancer Center at University of, Phone: 859-257-3379

Tulane Cancer Center Office of Clinical Research, Alexandria, Louisiana 71315-3198, United States; Recruiting
Clinical Trials Office - Tulane Cancer Center, Phone: 504-988-6121

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States; Recruiting
Joseph Wiley, Phone: 410-601-5864

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Clinical Trials Office - Dana-Farber/Harvard Cancer Center, Phone: 617-582-8480

Floating Hospital for Children at Tufts - New England Medical Center, Boston, Massachusetts 02111, United States; Recruiting
Cynthia S. Kretschmar, Phone: 617-636-5535

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Clinical Trials Office - Massachusetts General Hospital, Phone: 877-726-5130

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States; Recruiting
Clinical Trials Office - Barbara Ann Karmanos Cancer Institute, Phone: 313-576-9363

Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States; Recruiting
Clinical Trials Office - Breslin Cancer Center at Ingham Regio, Phone: 517-334-2765

Butterworth Hospital at Spectrum Health, Grand Rapids, Michigan 49503-2560, United States; Recruiting
David S. Dickens, Phone: 616-391-2086

Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States; Recruiting
Clincial Trials Office - Van Elslander Cancer Center at St. Jo, Phone: 313-343-3166

Masonic Cancer Center at University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Clinical Trials Office - Masonic Cancer Center at University o, Phone: 612-624-2620

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States; Recruiting
Gail C. Megason, Phone: 601-984-5220

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Maxine Hetherington, Phone: 816-234-3265

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States; Recruiting
Clinical Trials Office - Hackensack University Medical Center, Phone: 201-996-2879

Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States; Recruiting
Clinical Trials Office - Newark Beth Israel Medical Center, Phone: 973-926-3136

Overlook Hospital, Morristown, New Jersey 07962, United States; Recruiting
Hazem Mahmoud, Phone: 973-971-6720

St. Joseph's Hospital and Medical Center, Paterson, New Jersey 07503, United States; Recruiting
Mary Ann Bonilla, Phone: 973-754-3349

Westmead Institute for Cancer Research at Westmead Hospital, Westmead, New South Wales 2145, Australia; Recruiting
Geoffrey McCowage, Phone: 61298452122

Albany Medical Center Hospital, Albany, New York 12208-3419, United States; Recruiting
Vikramjit S. Kanwar, Phone: 518-262-5513x25265

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, Phone: 212-305-8615

New York Medical College, Valhalla, New York 10595, United States; Recruiting
Fevzi Ozkaynak, Phone: 914-493-7997

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States; Recruiting
Clinical Trials Office - SUNY Upstate Medical University Hospi, Phone: 315-464-5476

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States; Recruiting
Clinical Trials Office - Blumenthal Cancer Center at Carolinas, Phone: 704-355-2884

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States; Recruiting
Clinical Trials Office - Duke Comprehensive Cancer Center, Phone: 888-275-3853

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States; Recruiting
Clinical Trials Office - Lineberger Comprehensive Cancer Cente, Phone: 877-668-0683; 919-966-4432

IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada; Recruiting
Margaret C. Yhap, Phone: 902-470-8778

Akron Children's Hospital, Akron, Ohio 44308-1062, United States; Recruiting
Clinical Trials Office - Akron Children's Hospital, Phone: 330-543-3193

Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States; Recruiting
Emmett Broxson, Phone: 937-641-3111

Nationwide Children's Hospital, Columbus, Ohio 43205-2696, United States; Recruiting
Amanda Termuhlen, Phone: 614-722-3552

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
Rene Y. McNall-Knapp, Phone: 405-271-5311

Legacy Emanuel Hospital and Health Center and Children's Hospital, Portland, Oregon 97227, United States; Recruiting
Clinical Trials Office - Legacy Emanuel Hospital and Health Ce, Phone: 503-413-8199

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Clinical Trials Office - Children's Hospital of Pittsburgh, Phone: 412-692-5573

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States; Recruiting
Clinical Trials Office - Penn State Cancer Institute at Milton, Phone: 717-531-3779, Email: CTO@hmc.psu.edu

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States; Recruiting
Clinical Trials Office - St. Christopher's Hospital for Childr, Phone: 215-427-8991

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada; Recruiting
Yvan Samson, Phone: 514-345-4969

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada; Recruiting
Sharon Abish, Phone: 514-412-4400x22219

Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada; Recruiting
Kaiser Ali, Phone: 306-655-2744

Greenville Hospital Cancer Center, Greenville, South Carolina 29605, United States; Recruiting
Clinical Trials Office - Greenville Hospital Cancer Center, Phone: 864-241-6251

Sanford Cancer Center at Sanford USD Medical Center, Sioux Falls, South Dakota 57117-5039, United States; Recruiting
Clinical Trials Office - Sanford Cancer Center, Phone: 605-328-1367

East Tennessee Children's Hospital, Knoxville, Tennessee 37901, United States; Recruiting
Ray C. Pais, Phone: 865-541-8266

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States; Recruiting
Clinical Trials Office - Cook's Children's Medical Center, Phone: 682-885-2103

Driscoll Children's Hospital, Corpus Christi, Texas 78411, United States; Recruiting
Clinical Trials Office - Driscoll Children's Hospital, Phone: 361-694-5311

Medical City Dallas Hospital, Dallas, Texas 75230, United States; Recruiting
Carl Lenarsky, Phone: 972-566-6647x4439

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States; Recruiting
Michael S. Grimley, Phone: 210-575-7268

Texas Tech University Health Sciences Center School of Medicine - Amarillo, Amarillo, Texas 79106, United States; Recruiting
Curtis W. Turner, Phone: 806-354-5434X264

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States; Recruiting
Paul Thomas, Phone: 210-704-2187

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States; Recruiting
Douglas Hawkins, Phone: 206-987-3096

Providence Cancer Center at Sacred Heart Medical Center, Spokane, Washington 99220-2555, United States; Recruiting
Judy Felgenhauer, Phone: 509-474-2777

West Virginia University Health Sciences Center - Charleston, Charleston, West Virginia 25302, United States; Recruiting
Elizabeth Kurczynski, Phone: 304-388-1540

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia; Recruiting
Catherine Cole, Phone: 011-6189340-8238

Midwest Children's Cancer Center at Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Bruce M. Camitta, Phone: 414-456-4106

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2004
Last updated: November 1, 2008