OBJECTIVES:
Primary
- To maintain the overall survival (as defined by 4-year "second-event"-free survival) at or above 95% for pediatric patients with high-risk Hodgkin lymphoma (HL).
Secondary
- To maintain 3-year event-free survival at or above 93% for patients with high-risk HL.
- To maintain comparable overall survival (as defined by 4-year "second-event"-free survival) between patients with high-risk HL who have a rapid or slow response to the initial 2 courses of ABVE-PC chemotherapy by intensifying therapy through the addition of 2 courses of ifosfamide/vinorelbine in those with a slow early response.
- To investigate whether very early response assessment measured by FDG-PET scan after 1 course of ABVE-PC chemotherapy identifies a patient cohort that can be studied in future trials and that is distinguishable from currently defined rapid early response after 2 courses.
- To describe the patterns of relapse after ABVE-PC chemotherapy and risk-adapted radiotherapy.
OUTLINE: This is a multicenter study.
- Induction therapy (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
NOTE: *Patients do not receive filgrastim on day 8.
Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.
- Consolidation therapy: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy.
- Regimen I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
- Regimen II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.
- Risk-adapted radiotherapy: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression.
After completion of study therapy, patients are followed up periodically for 10 years.
DISEASE CHARACTERISTICS:
- Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria:
- Classical disease
- Nodular lymphocyte-predominant disease
- Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following:
- Unexplained weight loss > 10% within the past 6 months
- Unexplained recurrent fever > 38°C within the past month
- Recurrent drenching night sweats within the past month
PATIENT CHARACTERISTICS:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 to 5 months)
- 0.5 mg/dL (6 to 11 months)
- 0.6 mg/dL (12 to 23 months)
- 0.8 mg/dL (2 to 5 years)
- 1 mg/dL (6 to 9 years)
- 1.2 mg/dL (10 to 12 years)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years)
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 2.5 times ULN for age
- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by MUGA (unless due to large mediastinal mass from HL)
- FEV_1/FVC > 60% by pulmonary function tests (PFT) (unless due to large mediastinal mass from HL)
- For children who are unable to cooperate for PFTs, the criteria are:
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 92% on room air
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No pathologic prolongation of QTc interval (> 450 milliseconds) on 12-lead ECG
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, biological response modifiers (e.g., monoclonal antibody therapy), or radiotherapy
- At least 28 days since prior corticosteroids except for emergent treatment for respiratory distress or spinal cord compression, or for treatment of allergy to contrast agent required for CT scan
- No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
- Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic reactions allowed
- No concurrent pegfilgrastim
Last updated: 08/03/2012
NCT ID: NCT01026220
IRB Number:09-008517
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