Clinical trial NCT00005578: Combination Chemotherapy With or Without Dexrazoxane in Treating Children With Hodgkin's Disease
Official title: Advanced Stage Hodgkins Disease - A Pediatric Oncology Group Phase III Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Toxicity
Lymphoma
Keywords: stage II childhood Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
cardiac toxicity
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-26
Enrollment: 219
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without dexrazoxane in treating children who have Hodgkin's disease.

Detailed description: OBJECTIVES: I. Determine the efficacy of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (DBVE-PC) with filgrastim (G-CSF) followed by consolidative radiotherapy in children with advanced stage Hodgkin's disease. II. Tailor therapy based on rapidity of response in order to minimize cumulative drug dosages. III. Compare the efficacy of dexrazoxane in reducing pulmonary and cardiac toxicity of DBVE-based therapy without compromising response.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin and etoposide on days 0 and 1, bleomycin and vincristine on days 0 and 7, cyclophosphamide on day 0, and prednisone on days 0-6. Filgrastim (G-CSF) is administered on days 5-6 and 8-19. Each course is 21 days in length. Patients assigned to arm I receive only these drugs. Patients assigned to arm II receive dexrazoxane on days 0, 1, and 7 in addition to therapy as in arm I. Patients who exhibit a complete remission (CR) or provisional CR then receive radiotherapy to the regional field 5 days a week for 2.8 weeks. If the disease is not responsive, 2 more courses of chemotherapy are given. Patients whose disease remains nonresponsive or progresses go off the study. Radiotherapy may follow for others. Patients are followed every 3 months for the first year, every 4 months for the second year, every 6 months for the third year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 277 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven Hodgkin's disease of the following stages: Stages IIB, IIIB or IV

PATIENT CHARACTERISTICS: Age: 21 or under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 2 times upper normal limit Renal: Not specified Other: Not pregnant

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: Less than one week of steroids for management of airway complications Radiotherapy: No prior radiotherapy except emergency radiation to the mediastinum Surgery: Not specified

Primary outcomes:
measure: Diffusing capacity of the lungs for carbon monoxide (DLCO)
timeFrame: One year post therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Mobile
country: United States
facility: MBCCOP - University of South Alabama
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital and Clinics, University of Florida
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Tampa
country: United States
facility: CCOP - Florida Pediatric
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Children's Memorial Hospital, Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Boston Floating Hospital Infants and Children
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Memorial Mission Hospital
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Healthcare
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University School of Medicine
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Memorial Hospital
state: Oklahoma
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Children's Hospital of Greenville Hospital System
state: South Carolina
city: Memphis
country: United States
facility: Saint Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: MBCCOP - South Texas Pediatric
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Charlottesville
country: United States
facility: Cancer Center, University of Virginia HSC
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center, Portsmouth
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Division
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Bern
country: Switzerland
facility: Swiss Pediatric Oncology Group Bern
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Cindy Schwartz, MD
role: STUDY_CHAIR
References:
citation: Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, Mendenhall NP, Sposto R, Chauvenet A, Schwartz CL. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol. 2007 Feb 10;25(5):493-500. doi: 10.1200/JCO.2005.02.3879.
citation: Schwartz CL, Tebbi CK, Constine LS: Response based therapy for pediatric Hodgkin's disease (HD): Pediatric Oncology Group (POG) protocols 9425/9426. [Abstract] Med Pediatr Oncol 37 (3): A-P219, 263, 2001.
citation: Voss SD, Chen L, Constine LS, Chauvenet A, Fitzgerald TJ, Kaste SC, Slovis T, Schwartz CL. Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin's lymphoma: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2635-40. doi: 10.1200/JCO.2011.40.7841. Epub 2012 Jun 11.
citation: Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. doi: 10.1182/blood-2008-10-184143. Epub 2009 Jul 7.
citation: Constine LS, Marcus R, Chauvenet A, et al.: Patterns of failure after response-based, dose-dense therapy for intermediate/high risk pediatric Hodgkin's disease (POG 9425). [Abstract] Int J Radiat Oncol Biol Phys 63 (Suppl 1): A-37, S21, 2005.
citation: Schwartz CL, Constine LS, London W, et al.: POG 9425: response-based, intensively timed therapy for intermediate/high stage (IS/HS) pediatric Hodgkin's disease. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1555, 2002.