A Phase II Study of IGEV +/- Bortezomib Before Hign Dose Consolidation in Relapsed/Refractory Hodgkin's Lymphoma

IGEV +/- Bortezomib (Velcade) as Induction Before High Dose Consolidation in Relapsed/Refractory Hodgkin's Lymphoma After First Line Treatment: a Randomized Phase II Trial. On Behalf of Intergruppo Italiano Linfomi

The purpose of this study is to evaluate if the addition of Bortezomib (Velcade) to IGEV combination (Ifosfamide, Gemcitabine and Vinorelbine) in patients with relapsed/refractory Hodgkin's lymphoma increases the rate of complete remission (PET negativity) at transplantation.

Inclusion Criteria:

• Diagnosis of Hodgkin's lymphoma failing or relapsing after first-line chemotherapy (MOPP/AVBD , MOPP/EBV/CAD and analogs are considered one line)
• Age >18 and <65 years
• Signed informed consent
• If female, patient is either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control
• If male, patient agrees to use an acceptable barrier method for contraception
• ECOG performance status <2
• Platelet count >100.000/mmc
• Hemoglobin >7.5 g/dL
• Absolute neutrophil count (ANC) >1.500/mmc
• Serum calcium <3.5 mmol/L (<14 mg/dL)
• AST/ALT: <2.5 x the ULN
• Total bilirubin: <1.5 x the ULN

Exclusion Criteria:

• Previous treatment with velcade
• Nitrosoureas within 6 weeks or any other chemotherapy within 3 weeks before enrollment
• Immunotherapy or antibody therapy within 4 weeks before enrollment
• Experimental drug or medical device within 4 weeks before start of treatment
• Major surgery within 4 weeks before enrollment
• History of allergic reaction attributable to compounds containing boron or mannitol or any of the drugs in the IGEV regimen
• Peripheral neuropathy of NCI CTCAE Grade 2 or higher
• Myocardial infarction within 6 months of enrollment or NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances including diabetes mellitus
• Need for therapy with concomitant CYP 3A4 inhibitors or inducers
• HIV-positive, if known
• Hepatitis B surface antigen-positive or active hepatitis C infection, if known
• Active systemic infection requiring treatment
• If female, pregnancy or breast-feeding.