Combination Chemotherapy in Treating Young Male Patients With Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well combination chemotherapy works in treating young male patients with Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the safety and efficacy of combination chemotherapy comprising vincristine, etoposide, cyclophosphamide, vinblastine, prednisone, and doxorubicin hydrochloride (VECOPA) in pediatric male patients with previously untreated stage II-IV classic Hodgkin's lymphoma. Compare the effects of VECOPA vs cyclophosphamide, vincristine, procarbazine hydrochloride, and prednisone (COPP) in these patients. OUTLINE: This is a pilot, multicenter study. Patients are stratified according to disease stage (IA/B[E], IIA[E], IIB, or IIIA vs IIB[E], IIIA/B[E], IIIB, or IVA/B). Stratum 1 (stages IA/B[E], IIA[E], IIB, or IIIA): Patients receive oral prednisone on days 1-15, vincristine IV on days 1, 8, and 15, doxorubicin hydrochloride IV over 4 hours on days 1 and 15, and etoposide IV over 2 hours on days 2-6 (OEPA). Treatment repeats every 4 weeks for 2 courses. Beginning at week 9, patients receive VECOPA chemotherapy comprising oral prednisone on days 1-14 and 21-34, etoposide IV over 2 hours on days 1-3, doxorubicin hydrochloride IV over 2 hours on day 21, vinblastine IV and cyclophosphamide IV over 1 hour on days 1 and 21, and vincristine IV on days 8 and 29. Patients then undergo radiotherapy. Stratum 2 (stages IIB[E], IIIA/B[E], IIIB, or IVA/B): Patients receive 2 courses of OEPA as in stratum 1 followed by 2 courses of VECOPA (6-week courses). Patients then undergo radiotherapy. After completion of study treatment, patients are followed periodically for at least 6 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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Pilot Study for Therapy Optimising for Hodgkin's Lymphoma in Childhood and Adolescence; Optimising Therapy for Boys With Hodgkin's Lymphoma in Intermediate and Advanced Stages. Safety and Efficacy Study for Drug Combination VECOPA

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: prednisone
* Drug: vinblastine sulfate
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of classic Hodgkin's lymphoma (HL) Intermediate or advanced disease (stage I[E]-IV) No lymphocyte-predominant HL Previously untreated disease PATIENT CHARACTERISTICS: Male No known hypersensitivity or contraindication to study drugs No other concurrent malignancies No severe concurrent diseases (e.g., immune deficiency syndrome) No known HIV positivity PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy More than 30 days since prior and no other concurrent investigational drugs More than 30 days since prior and no concurrent participation in another clinical trial

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VECOPA<br>dose and time intensified consoloditation chemotherapy cycle | Drug: cyclophosphamide<br>* 1250 mg/m2 i.v. 60 Min.-Inf. day 1 and 21<br>Drug: doxorubicin hydrochloride<br>* 25mg/m²/day, 2 hours i.v.infusion on day 21<br>Drug: etoposide<br>* 150 mg/m²/day, 2 hours i.v.infusion (intravenous drip) on days 1 - 3<br>Drug: prednisone<br>* 40 mg/m2/day p.o. (intake by mouth)divided in 3 single doses daily from day 1 - 14 and day 21 - 34<br>Drug: vinblastine sulfate<br>* 6 mg/m² i.v. bolus on day 1 and day 21<br>Drug: vincristine sulfate<br>* 1,5 mg/m2 i.v. bolus max. single dose 2 mg (cap dose at 2 mg) on day 8 and day 29<br>Radiation: radiation therapy<br>* involved field irradiation, single daily fractions 1,5 Gy to max. 1,8 Gy standard dose 20 Gy, max dose 30 Gy (boost irradiation if required)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity at days 21 and 42 (+/- 2 days) of treatment | number of VECOPA cycles that allow continuation of chemotherapy on a sufficient hematopoietic recovery | days 21 and 42 (+/- 2 days) of treatment after start of VECOPA cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  | event-free survival at 5 years | 
| Overall survival |  | overall survival at 5 years | 

 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 III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, childhood lymphocyte depletion Hodgkin lymphoma, childhood mixed cellularity Hodgkin lymphoma, childhood nodular sclerosis Hodgkin lymphoma