Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Disease

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy with radiation therapy may kill more cancer cells. It is not yet known if chemotherapy is more effective with or without dexrazoxane for Hodgkin's disease. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy, with or without dexrazoxane, followed by radiation therapy in treating young patients with newly diagnosed stage I, stage II, or stage III Hodgkin's disease.

Detailed Description
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OBJECTIVES: I. Modify chemotherapy courses based on initial response to therapy in children with newly diagnosed stage IA/IIA/IIIA1 Hodgkin's disease. II. Examine the activity of variable courses of doxorubicin, bleomycin, vincristine, and etoposide (DBVE) followed by low-dose involved-field irradiation in these patients. III. Monitor the safety and feasibility of the response-dependent approach and the morbidity and immediate and long-term toxic effects associated with this regimen. IV. Assess whether limited therapy is adequate for patients with an early response. V. Evaluate whether the addition of dexrazoxane can reduce pulmonary toxicity while not significantly reducing the response rate or event-free survival. VI. Evaluate whether the frequency and magnitude of myocardial injury during therapy, as measured by elevated serum cardiac troponin-T, is reduced by the addition of dexrazoxane. OUTLINE: This is a randomized study. Patients are stratified by participating institution. Patients are randomly assigned to receive doxorubicin, bleomycin, vincristine, etoposide, and filgrastim with vs. without dexrazoxane. Filgrastim SC begins on days 6-13; no filgrastim is given on day 14 or 15. Filgrastim will restart 2 days after completing therapy and continue until count recovery from expected nadir (ANC greater than 1000 cubic meter after nadir). Courses repeat every 28 days. Those with stable or responding disease after 2-4 courses receive involved-field radiotherapy 5 days per week for 3.5 weeks. Tanner stage IV/V patients are eligible for randomization based on a front-end institutional agreement and may receive standard-field radiotherapy 5 days per week for up to 11 weeks at the investigator's discretion. Patients are followed yearly until relapse, death, or for a minimum of 10 years. PROJECTED ACCRUAL: A total of 285 patients will be accrued for this study over 5 years.

Official Title
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RESPONSE DEPENDENT TREATMENT OF STAGES IA, IIA AND IIIA HODGKIN'S DISEASE WITH DBVE AND LOW DOSE INVOLVED FIELD IRRADIATION WITH OR WITHOUT ZINECARD: A PEDIATRIC ONCOLOGY GROUP PHASE III STUDY

Conditions
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Cardiac Toxicity, Lymphoma

Intervention / Treatment
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* Biological: bleomycin sulfate
* Biological: filgrastim
* Drug: dexrazoxane hydrochloride
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: vincristine sulfate
* Radiation: low-LET cobalt-60 gamma ray therapy
* Radiation: low-LET electron therapy
* Radiation: low-LET photon therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven Hodgkin's disease No more than 5 weeks since diagnostic biopsy No B symptoms Clinical/pathologic stages (all histologies) as follows: Stage IA/IIA with mediastinal mass less than one third of chest diameter Stage IIIA limited to spleen or splenic, celiac, or portal nodes and lesions no larger than 6 cm Surgical staging required if: Clinical and imaging findings equivocal Tanner stage IV/V for whom radiotherapy is planned Concurrent registration on protocols POG-8828 (late effects study) and POG- 8829 (epidemiology study) required PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Hematopoietic: No hematopoietic disease Hepatic: No liver disease Renal: No renal disease Other: No severe organ or system damage or failure No pregnant or nursing women PRIOR CONCURRENT THERAPY: No prior therapy

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment #1 (Without Zinecard)<br>All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( < 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). | Biological: bleomycin sulfate<br>* Given IV<br>* Other names: NSC #125066;Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: etoposide<br>* Given IV<br>* Other names: NSC #141540;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;Radiation: low-LET cobalt-60 gamma ray therapy<br> <br> Radiation: low-LET electron therapy<br> <br> Radiation: low-LET photon therapy<br> <br> |
| Experimental: Treatment #2 (with Zinecard)<br>Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 | Biological: bleomycin sulfate<br>* Given IV<br>* Other names: NSC #125066;Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: dexrazoxane hydrochloride<br>* Given IV<br>* Other names: NSC #169780;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: etoposide<br>* Given IV<br>* Other names: NSC #141540;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;Radiation: low-LET cobalt-60 gamma ray therapy<br> <br> Radiation: low-LET electron therapy<br> <br> Radiation: low-LET photon therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLCO | The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms. | 1 year post therapy | 

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