A Phase III Groupwide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease
A Phase III Groupwide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease
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. 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.
OBJECTIVES:
I. To compare response-based therapy to standard therapy for intermediate risk Hodgkin disease.
II. To determine whether involved field radiation therapy (IFRT) can be eliminated based upon early and complete response to multiagent chemotherapy.
III. To determine whether the addition of an additional two cycles of chemotherapy (DECA) can improve outcome in those with a slow early response to standard chemotherapy.
IV. To prospectively collect information on the individual prognostic significance of the following presenting factors: erythrocyte sedimentation rate, circulating levels of IL-10, each of the "B" symptoms - fever, night sweats, weight loss, nodal aggregate > 6 cm, large mediastinal mass > 1/3 thoracic diameter and number of involved nodal sites, histology, albumin, blood counts, sex and age.
V. To study the reliability and utility of [18F] -Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging modality in Hodgkin disease.
VI. To determine the frequency and severity of late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant neoplasms.
VII. To serve as the therapeutic companion to biology studies in Hodgkin disease and correlate those results with response to therapy, event free-survival and overall survival.
OUTLINE: This is a randomized, multicenter study.
ARM I (ALL PATIENTS-OFF THERAPY BEFORE CALLBACK-INDUCTION CHEMOTHERAPY [ABVE-PC]): Patients receive doxorubicin intravenously (IV) over 10-30 minutes on days 1-2, bleomycin sulfate 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 2 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 receive 2 additional courses of ABVE-PC chemotherapy. After completion of treatment, patients are randomized to 1 of 4 treatment arms.
ARM II: Patients with sustained complete response (CR) undergo involved field radiation therapy (IFRT) approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.
ARM III: Patients with sustained CR receive no further treatment.
ARM IV: Patients with very good partial response (VGPR), partial response (PR) or stable disease (SD) undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.
ARM V: Patients with progressive disease are taken off therapy and treated their physician's discretion.
SER: Patients are randomized to 1 of 2 treatment arms.
ARM VI: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, cytarabine IV over 3 hours on days 1-2, and receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and 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.
ARM VII: Patients receive 2 courses of ABVE-PC chemotherapy.
In both SER arms, patients with sustained CR or PR undergo IFRT approximately 3 weeks after the last course of chemotherapy.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Inclusion Criteria:
Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:
May not be staged by laparotomy alone
Bilirubin no greater than 1.5 times normal
SGOT or SGPT less than 2.5 times normal
Creatinine no greater than 1.5 times normal
Creatinine clearance greater than 40 mL/min
Radioisotope glomerular filtration rate greater than 70 mL/min
Shortening fraction at least 27% by echocardiogram
Ejection fraction at least 50% by MUGA
No pathologic prolongation of QTc interval on 12-lead electrocardiogram
FEV_1/FVC greater than 60% by pulmonary function test
Pulse oximetry greater than 94%
No evidence of dyspnea at rest
No exercise intolerance
Adequate venous access
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior chemotherapy
At least 1 month since prior corticosteroids except prednisone for respiratory distress
No prior radiotherapy
Sacramento, California 95817, United States
Miami, Florida 33136, United States
Minneapolis, Minnesota 55404, United States
New Brunswick, New Jersey 08903, United States
New Hyde Park, New York 11040, United States
Houston, Texas 77030, United States
Spokane, Washington 99204, United States
Petah Tikua, 49202, Israel