Combination Chemotherapy With or Without Dexrazoxane in Treating Children With Hodgkin's Disease

Lymphoma Clinical Trial

Official title:

Advanced Stage Hodgkins Disease - A Pediatric Oncology Group Phase III Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005578
• Other study ID #: 9425
• Secondary ID: COG-9425CDR00000
• Status: Completed
• Phase: Phase 3
• First received: May 2, 2000
• Last updated: July 23, 2014
• Start date: March 1997
• Est. completion date: June 2008

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: June 2008
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Toxicity
• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• bleomycin sulfate

• filgrastim

Drug:
• cyclophosphamide

• dexrazoxane hydrochloride

• doxorubicin hydrochloride

• etoposide

• prednisone

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McMaster Division	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
United States	Memorial Mission Hospital	Asheville	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Cancer Center, University of Virginia HSC	Charlottesville	Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego Cancer Center	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	MBCCOP - University of South Alabama	Mobile	Alabama
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Massey Cancer Center	Richmond	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	MBCCOP - South Texas Pediatric	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	CCOP - Florida Pediatric	Tampa	Florida
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

References & Publications (6)

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.

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.

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 lymph — View 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.

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. — View 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 Onc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diffusing capacity of the lungs for carbon monoxide (DLCO)	The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.	One year post therapy	No