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

NCT00005578 | Completed Phase 3 DMC

• 4 other identifiers: 9425COG-9425CDR0000065359P9425
• Study Type: interventional
• Target: 219
• Locations: 3 countries
• Sites: 63

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Arm 1

EXPERIMENTAL

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.

Biological: bleomycin sulfate; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: vincristine sulfate; Radiation: radiation therapy

Arm 2

EXPERIMENTAL

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

Biological: bleomycin sulfate; Biological: filgrastim; Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: vincristine sulfate; Radiation: radiation therapy

Interventions

bleomycin sulfate BIOLOGICAL

Also known as: Blenoxane, NSC #125066

Arm 1; Arm 2

filgrastim BIOLOGICAL

Also known as: GRANULOCYTE-COLONY STIMULATING FACTOR, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629

Arm 1; Arm 2

cyclophosphamide DRUG

Also known as: CTX, Cytoxan, NSC #26271

Arm 1; Arm 2

dexrazoxane hydrochloride DRUG

Also known as: DZR, ADR-529, ZINECARD, ICRF-187, NSC #169780

Arm 2

doxorubicin hydrochloride DRUG

Also known as: Adriamycin, NSC #123127

Arm 1; Arm 2

etoposide DRUG

Also known as: VP-16, VePesid, NSC #141540

Arm 1; Arm 2

prednisone DRUG

Also known as: Deltasone, Meticorten, Liquid Pred, NSC #10023

Arm 1; Arm 2

vincristine sulfate DRUG

Also known as: VCR, Oncovin, NSC #67574

Arm 1; Arm 2

radiation therapy RADIATION

Arm 1; Arm 2

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (63)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

MBCCOP - University of South Alabama

Mobile, Alabama, 36688, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Yale Comprehensive Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5000, United States

Location

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, 32610-100277, United States

Location

Sylvester Cancer Center, University of Miami

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

CCOP - Florida Pediatric

Tampa, Florida, 33682-7757, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Children's Memorial Hospital, Chicago

Chicago, Illinois, 60614, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

MBCCOP - LSU Medical Center

New Orleans, Louisiana, 70112, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Ochsner Clinic

New Orleans, Louisiana, 70121, United States

Location

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231, United States

Location

Boston Floating Hospital Infants and Children

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

CCOP - Northern New Jersey

Hackensack, New Jersey, 07601, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11042, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Rochester Cancer Center

Rochester, New York, 14642, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Memorial Mission Hospital

Asheville, North Carolina, 28801, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Healthcare

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

East Carolina University School of Medicine

Greenville, North Carolina, 27858-4354, United States

Location

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157-1082, United States

Location

Oklahoma Memorial Hospital

Oklahoma City, Oklahoma, 73126-0307, United States

Location

CCOP - Columbia River Program

Portland, Oregon, 97213, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

Children's Hospital of Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105-2794, United States

Location

Simmons Cancer Center - Dallas

Dallas, Texas, 75235-9154, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MBCCOP - South Texas Pediatric

San Antonio, Texas, 78284-7810, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Cancer Center, University of Virginia HSC

Charlottesville, Virginia, 22908, United States

Location

Naval Medical Center, Portsmouth

Portsmouth, Virginia, 23708-2197, United States

Location

Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

McMaster Division

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Swiss Pediatric Oncology Group Bern

Bern, CH 3010, Switzerland

Location

Related Publications (6)

• 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.

  PMID: 17290056 BACKGROUND

• 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.

  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.

  PMID: 22689804 RESULT

• 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.

  PMID: 19584400 RESULT

• 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.

  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.

  RESULT

MeSH Terms

Conditions

Cardiotoxicity; Lymphoma

Interventions

Bleomycin; Filgrastim; Granulocyte Colony-Stimulating Factor; Cyclophosphamide; Dexrazoxane; Razoxane; Doxorubicin; Etoposide; Prednisone; Vincristine; Radiotherapy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Therapeutics

Study Officials

• Cindy Schwartz, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2000
• First Posted: May 26, 2004
• Study Start: March 1, 1997
• Primary Completion: October 1, 2004
• Study Completion: June 1, 2008
• Last Updated: July 24, 2014

Record last verified: 2014-07

Locations

CA (5); US (57); CH (1)