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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005578
First received: May 2, 2000
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Cardiac Toxicity
Lymphoma
Biological: bleomycin sulfate
Biological: filgrastim
Drug: cyclophosphamide
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: Advanced Stage Hodgkins Disease - A Pediatric Oncology Group Phase III Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) [ Time Frame: One year post therapy ] [ Designated as safety issue: No ]
    The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.


Enrollment: 219
Study Start Date: March 1997
Study Completion Date: June 2008
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: bleomycin sulfate
Other Names:
  • Blenoxane
  • NSC #125066
Biological: filgrastim
Other Names:
  • GRANULOCYTE-COLONY STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Radiation: radiation therapy
Experimental: 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
Biological: bleomycin sulfate
Other Names:
  • Blenoxane
  • NSC #125066
Biological: filgrastim
Other Names:
  • GRANULOCYTE-COLONY STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
Drug: dexrazoxane hydrochloride
Other Names:
  • DZR
  • ADR-529
  • ZINECARD
  • ICRF-187
  • NSC #169780
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #10023
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
Radiation: radiation therapy

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

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005578

  Show 63 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Cindy Schwartz, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
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, 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.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00005578     History of Changes
Other Study ID Numbers: 9425, COG-9425, CDR0000065359, P9425
Study First Received: May 2, 2000
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
stage II childhood Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
cardiac toxicity

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bleomycin
Cyclophosphamide
Dexrazoxane
Doxorubicin
Etoposide
Etoposide phosphate
Lenograstim
Liposomal doxorubicin
Prednisone
Razoxane
Vincristine
Adjuvants, Immunologic
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Cardiotonic Agents

ClinicalTrials.gov processed this record on October 23, 2014