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

Study Overview
=================
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.

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

Conditions
-----------------
Cardiac Toxicity, Lymphoma

Intervention / Treatment
-----------------
* Biological: bleomycin sulfate
* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: dexrazoxane hydrochloride
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: prednisone
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>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<br> <br> * Other names: NSC #125066;Biological: filgrastim<br> <br> * Other names: NSC #614629;Drug: cyclophosphamide<br> <br> * Other names: NSC #26271;Drug: doxorubicin hydrochloride<br> <br> * Other names: NSC #123127;Drug: etoposide<br> <br> * Other names: NSC #141540;Drug: prednisone<br> <br> * Other names: NSC #10023;Drug: vincristine sulfate<br> <br> * Other names: NSC #67574;Radiation: radiation therapy<br> <br> |
| Experimental: Arm 2<br>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<br> <br> * Other names: NSC #125066;Biological: filgrastim<br> <br> * Other names: NSC #614629;Drug: cyclophosphamide<br> <br> * Other names: NSC #26271;Drug: dexrazoxane hydrochloride<br> <br> * Other names: NSC #169780;Drug: doxorubicin hydrochloride<br> <br> * Other names: NSC #123127;Drug: etoposide<br> <br> * Other names: NSC #141540;Drug: prednisone<br> <br> * Other names: NSC #10023;Drug: vincristine sulfate<br> <br> * Other names: NSC #67574;Radiation: radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, cardiac toxicity