A Phase II Study of Bortezomib (Velcade, PS-341, IND #58443) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease

Inclusion Criteria:

- Histologically confirmed Hodgkin's lymphoma at time of relapse or disease
progression, meeting all of the following criteria:

- Stage I-IV disease

- No morphologically unclassifiable disease

- Meets 1 of the following criteria:

- Mixed cellularity

- Lymphocytic depletion (LD)

- LD, diffuse fibrosis

- LD, reticular

- Lymphocyte predominance (LP)

- LP, diffuse

- LP, nodular

- Nodular sclerosis (NS)

- NS, cellular phase

- NS, lymphocytic predominance

- NS, mixed cellularity

- NS, LD

- Not otherwise specified

- Primary refractory disease OR disease in first relapse, except for the following:

- Patients achieving a complete response after treatment on protocol COG-AHOD0431
who experience a biopsy-proven recurrence after doxorubicin hydrochloride,
vincristine, prednisone, and cyclophosphamide without involved-field
radiotherapy

- Patients on the observation-only arm of protocol COG-AHOD0431

- Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or
kidney)

- Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or
thrombocytopenia are allowed provided both of the following criteria are met:

- Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)

- Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)

- Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy
PS 60-100% (for patients =< 16 years of age)

- Life expectancy >= 2 months

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone
marrow involvement)

- Creatinine =< 1.5 times upper limit of normal (ULN)

- Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2

- AST and ALT =< 2.5 times ULN

- Bilirubin =< 1.5 times ULN

- Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide
study

- Patients with a seizure disorder are eligible if on a nonenzyme-inducing
anticonvulsant and seizures are well controlled

- No CNS toxicity > grade 2

- No serious intercurrent illnesses

- No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any
component of the study drugs

- No peripheral neuropathy > grade 1

- No known hypersensitivity to bortezomib, boron, or mannitol

- No other concurrent chemotherapy or immunomodulating agents (including steroids)

- Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic
reactions

- No dexamethasone or aprepitant as an antiemetic

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Recovered from prior therapy

- No prior bortezomib or other proteasome inhibitors

- At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)

- More than 14 days since prior investigational drugs

- No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including
phenytoin, carbamazepine, phenobarbital, or other anticonvulsants

- Benzodiazepine or gabapentin allowed