search
Back to results

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

Primary Purpose

Cardiac Toxicity, Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
bleomycin sulfate
filgrastim
cyclophosphamide
dexrazoxane hydrochloride
doxorubicin hydrochloride
etoposide
prednisone
vincristine sulfate
radiation therapy
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Toxicity focused on measuring stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, cardiac toxicity

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama Comprehensive Cancer Center
  • MBCCOP - University of South Alabama
  • University of Arkansas for Medical Sciences
  • University of California San Diego Cancer Center
  • Lucile Packard Children's Hospital at Stanford
  • University of California Davis Medical Center
  • Yale Comprehensive Cancer Center
  • Walter Reed Army Medical Center
  • Shands Hospital and Clinics, University of Florida
  • Sylvester Cancer Center, University of Miami
  • Miami Children's Hospital
  • CCOP - Florida Pediatric
  • Emory University Hospital - Atlanta
  • Cancer Research Center of Hawaii
  • Children's Memorial Hospital, Chicago
  • University of Kansas Medical Center
  • CCOP - Wichita
  • MBCCOP - LSU Medical Center
  • CCOP - Ochsner
  • Ochsner Clinic
  • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Johns Hopkins Oncology Center
  • Boston Floating Hospital Infants and Children
  • Dana-Farber Cancer Institute
  • University of Massachusetts Memorial Medical Center
  • Children's Hospital of Michigan
  • University of Mississippi Medical Center
  • Cardinal Glennon Children's Hospital
  • Washington University School of Medicine
  • CCOP - Northern New Jersey
  • Hackensack University Medical Center
  • Roswell Park Cancer Institute
  • Schneider Children's Hospital
  • Mount Sinai School of Medicine
  • University of Rochester Cancer Center
  • State University of New York - Upstate Medical University
  • Memorial Mission Hospital
  • Carolinas Medical Center
  • Presbyterian Healthcare
  • Duke Comprehensive Cancer Center
  • East Carolina University School of Medicine
  • Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
  • Oklahoma Memorial Hospital
  • CCOP - Columbia River Program
  • St. Christopher's Hospital for Children
  • Rhode Island Hospital
  • Medical University of South Carolina
  • Children's Hospital of Greenville Hospital System
  • Saint Jude Children's Research Hospital
  • Simmons Cancer Center - Dallas
  • Baylor College of Medicine
  • MBCCOP - South Texas Pediatric
  • University of Texas Health Science Center at San Antonio
  • Cancer Center, University of Virginia HSC
  • Naval Medical Center, Portsmouth
  • Massey Cancer Center
  • Midwest Children's Cancer Center
  • Cross Cancer Institute
  • McMaster Division
  • Hospital for Sick Children
  • Montreal Children's Hospital
  • Hopital Sainte Justine
  • Swiss Pediatric Oncology Group Bern

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
May 2, 2000
Last Updated
July 23, 2014
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00005578
Brief Title
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

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 1997 (undefined)
Primary Completion Date
October 2004 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
Single
Allocation
Randomized
Enrollment
219 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
bleomycin sulfate
Other Intervention Name(s)
Blenoxane, NSC #125066
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
GRANULOCYTE-COLONY STIMULATING FACTOR, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CTX, Cytoxan, NSC #26271
Intervention Type
Drug
Intervention Name(s)
dexrazoxane hydrochloride
Other Intervention Name(s)
DZR, ADR-529, ZINECARD, ICRF-187, NSC #169780
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
Adriamycin, NSC #123127
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16, VePesid, NSC #141540
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
Deltasone, Meticorten, Liquid Pred, NSC #10023
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
VCR, Oncovin, NSC #67574
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Diffusing capacity of the lungs for carbon monoxide (DLCO)
Description
The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.
Time Frame
One year post therapy

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cindy Schwartz, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
MBCCOP - University of South Alabama
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36688
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Lucile Packard Children's Hospital at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Yale Comprehensive Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8028
Country
United States
Facility Name
Walter Reed Army Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20307-5000
Country
United States
Facility Name
Shands Hospital and Clinics, University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-100277
Country
United States
Facility Name
Sylvester Cancer Center, University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
CCOP - Florida Pediatric
City
Tampa
State/Province
Florida
ZIP/Postal Code
33682-7757
Country
United States
Facility Name
Emory University Hospital - Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Cancer Research Center of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Children's Memorial Hospital, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3882
Country
United States
Facility Name
MBCCOP - LSU Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
CCOP - Ochsner
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Ochsner Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Boston Floating Hospital Infants and Children
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
CCOP - Northern New Jersey
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Schneider Children's Hospital
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Rochester Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Memorial Mission Hospital
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28232-2861
Country
United States
Facility Name
Presbyterian Healthcare
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28233-3549
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
East Carolina University School of Medicine
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858-4354
Country
United States
Facility Name
Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1082
Country
United States
Facility Name
Oklahoma Memorial Hospital
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73126-0307
Country
United States
Facility Name
CCOP - Columbia River Program
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134-1095
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0721
Country
United States
Facility Name
Children's Hospital of Greenville Hospital System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-2794
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
MBCCOP - South Texas Pediatric
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7810
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
Cancer Center, University of Virginia HSC
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Naval Medical Center, Portsmouth
City
Portsmouth
State/Province
Virginia
ZIP/Postal Code
23708-2197
Country
United States
Facility Name
Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
McMaster Division
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Hopital Sainte Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Swiss Pediatric Oncology Group Bern
City
Bern
ZIP/Postal Code
CH 3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
17290056
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.
Results Reference
background
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.
Results Reference
background
PubMed Identifier
22689804
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.
Results Reference
result
PubMed Identifier
19584400
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. Erratum In: Blood. 2016 Jul 28;128(4):605.
Results Reference
result
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.
Results Reference
result
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs