| Inclusion Criteria: | 1) Study enrollment must occur within 28 days of diagnosis and staging. If more than 28 days elapse before study enrollment, restaging of disease is required prior to study enrollment to confirm eligibility. Therefore any imaging study that is > 28 days old must be repeated. If the surgical diagnosis is > 28 days old, but all staging imaging studies are within 28 days, the Children's Oncology Group (COG) Study Chair should be contacted to approve registration.
2) Study enrollment must take place within five (5) calendar days of beginning protocol therapy. If enrollment takes place before starting therapy, the date protocol therapy is projected to start must be no later than five (5) calendar days after enrollment.
3) All Stage IB, IIB, IAE, IIAE, IIIA, IIIAE, IIIAS, IIIAE+S, IVA, and IVAE regardless of bulk disease. Stage IA and IIA only with bulk disease.
4) Staging will be determined by the clinical stage. Surgically staged patients may be eligible if they also have pre-surgical clinical staging.
5) Must agree to all possible randomizations dictated by the study.
6) Age: 0-21 years inclusive.
7) Creatinine clearance or radioisotope GFR >/= 70ml/min/1.73m^2 Or A serum creatinine based on age/gender as follows: 1 mo to < 6 mos max. serum creat of 0.4 for male and female, 6 mos to < 1 yr max. serum creat of 0.5 for male and female, 1 to < 2yrs max. serum creat of 0.6 for male and female, 2 to <6 yrs max. serum creat of 0.8 for male and female, 6 to <10 yrs max. serum creat of 1 for male and female, 10 to < 13 yrs max. serum creat 1.2 for male and female, 13 to < 16 yrs max. serum creat of 1.5 for male and 1.4 for female, >/= 16 yrs max. serum creat of 1.7 for male and 1.4 for female.
8) Adequate liver function defined as: Total bilirubin </=1.5 x normal and SGOT (AST) or SGPT (ALT) < 2.5 x normal.
9) Adequate cardiac function defined as: shortening fraction of >/= 27% by echocardiogram or, if echocardiogram not feasible, ejection fraction of >/= 50% by radionuclide angiogram (MUGA), unless due to large mediastinal mass from Hodgkin Disease. The COG Study Chair approval required for entry onto protocol with shortening fraction of < 27%. No pathologic prolongation of QTc interval on 12 lead ECG.
10) Adequate pulmonary function defined as: FEV1/FVC > 60% by pulmonary function test, unless due to large mediastinal mass from Hodgkin Disease. The COG Study Chair's approval required for entry onto protocol with FEV1/FVC </= 60%. For children who cannot adequately perform PFTs, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94%. PFTs should not be attempted for children under the age of 7 years. Patients with other pre-existing cardiac or pulmonary abnormalities require Study Chair approval prior to being placed on therapy.
11) Adequate venous access is required. An Infusaport (portacath) is recommended, but nor required.
12) The patient and/or the patients legally authorized guardian must acknowledge in writing that consent to becoming a study subject has been obtained in accordance with institutional policies of the United States Health Department and Human Services.
13) Approval for the use of this treatment protocol by the individual institutions Human Rights Committee must be obtained in accordance with the institutional assurance policies of the United States Health Department and Human Services. |