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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hodgkin Disease

Intervention / Treatment
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* Drug: Ifosfamide, Gemcitabine, Vinorelbine
* Drug: Bortezomib + IGEV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>IGEV regimen (Ifosfamide, Gemcitabine, Vinorelbine) | Drug: Ifosfamide, Gemcitabine, Vinorelbine<br>* Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.<br>|
| Experimental: 2<br>B-IGEV (Bortezomib + IGEV) | Drug: Bortezomib + IGEV<br>* Bortezomib 1,3 mg/sqm, day 1, 4, 8; Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET negativity rate obtained with IGEV or B-IGEV will be compared |  | PET negativity after 4 courses of induction (IGEV or B-IGEV) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin disease, Salvage therapy, Bortezomib, Transplantation