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

NCT ID: NCT00005578

Last Updated: 2014-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

219 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-03-31

Study Completion Date

2008-06-30

Brief Summary

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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

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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.

Conditions

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Cardiac Toxicity Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Study Groups

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Arm 1

Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin hydrochloride and etoposide on days 0 and 1, bleomycin sulfate and vincristine sulfate 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.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Arm 2

Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin hydrochloride and etoposide on days 0 and 1, bleomycin sulfate and vincristine sulfate 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. Dexrazoxane hydrochloride on days 0, 1, and 7

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

dexrazoxane hydrochloride

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Interventions

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bleomycin sulfate

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

dexrazoxane hydrochloride

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Other Intervention Names

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Blenoxane NSC #125066 GRANULOCYTE-COLONY STIMULATING FACTOR r-metHuG-CSF G-CSF Neupogen NSC #614629 CTX Cytoxan NSC #26271 DZR ADR-529 ZINECARD ICRF-187 NSC #169780 Adriamycin NSC #123127 VP-16 VePesid NSC #141540 Deltasone Meticorten Liquid Pred NSC #10023 VCR Oncovin NSC #67574

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cindy Schwartz, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

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University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

MBCCOP - University of South Alabama

Mobile, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

Yale Comprehensive Cancer Center

New Haven, Connecticut, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, United States

Site Status

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

CCOP - Florida Pediatric

Tampa, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic

New Orleans, Louisiana, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Boston Floating Hospital Infants and Children

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Schneider Children's Hospital

New Hyde Park, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

University of Rochester Cancer Center

Rochester, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Memorial Mission Hospital

Asheville, North Carolina, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Presbyterian Healthcare

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

East Carolina University School of Medicine

Greenville, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Oklahoma Memorial Hospital

Oklahoma City, Oklahoma, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Children's Hospital of Greenville Hospital System

Greenville, South Carolina, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

MBCCOP - South Texas Pediatric

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Cancer Center, University of Virginia HSC

Charlottesville, Virginia, United States

Site Status

Naval Medical Center, Portsmouth

Portsmouth, Virginia, United States

Site Status

Massey Cancer Center

Richmond, Virginia, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

McMaster Division

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Swiss Pediatric Oncology Group Bern

Bern, , Switzerland

Site Status

Countries

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United States Canada Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 17290056 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type RESULT
PMID: 22689804 (View on PubMed)

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.

Reference Type RESULT
PMID: 19584400 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT

Other Identifiers

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COG-9425

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000065359

Identifier Type: OTHER

Identifier Source: secondary_id

P9425

Identifier Type: OTHER

Identifier Source: secondary_id

9425

Identifier Type: -

Identifier Source: org_study_id

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