Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.

PURPOSE: This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease.

Further Study Information

OBJECTIVES:

• Compare response-based therapy with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without dexamethasone, etoposide, cytarabine, cisplatin, and/or radiotherapy in children with intermediate-risk Hodgkin's lymphoma.

• Determine whether radiotherapy can be eliminated from this regimen based upon early and complete response to multiagent chemotherapy in these patients.

• Determine whether the addition of dexamethasone, etoposide, cytarabine, cisplatin, and filgrastim (G-CSF) improves outcome in those patients with a slow early response to standard chemotherapy.

• Compare the frequency and severity of late effects of this therapy, including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity, and second malignant neoplasms, in patients treated with these regimens.

• Correlate results from biology and late effects studies with response to therapy, event-free survival, and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study.

• Initial chemotherapy (ABVE-PC): Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 4 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease.

At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).

• RER: Patients with RER receive 2 additional courses of ABVE-PC chemotherapy. After the additional course, patients with less than a complete response undergo radiotherapy 5 days a week. Patients with a complete response are randomized to receive either radiotherapy or no further treatment.

• SER: Patients with SER are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2 and cisplatin IV over 6 hours on day 1. Patients also receive G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.

• Arm II: Patients receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5-5.5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed Hodgkin's lymphoma

• All histologies eligible

• Stage IB or IIB

• Stage IA with bulk disease

• Stage IIA with bulk disease

• Stage IIAE

• Stage IIIA

• Stage IVA

• May not be staged by laparotomy alone

• Surgically staged patients must also have presurgical staging

PATIENT CHARACTERISTICS:

Age:

• 21 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 1.5 times normal

• SGOT or SGPT less than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

• Creatinine clearance greater than 40 mL/min OR

• Radioisotope glomerular filtration rate greater than 70 mL/min

Cardiovascular:

• Shortening fraction at least 27% by echocardiogram OR

• Ejection fraction at least 50% by MUGA

• No pathologic prolongation of QTc interval on 12-lead electrocardiogram

Pulmonary:

• FEV_1/FVC greater than 60% by pulmonary function test OR

• Pulse oximetry greater than 94% AND

• No evidence of dyspnea at rest AND

• No exercise intolerance

Other:

• Adequate venous access

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• At least 1 month since prior corticosteroids except prednisone for respiratory distress

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Debra L. Friedman

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00025259
Information obtained from ClinicalTrials.gov on May 13, 2013

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