VELCADE in MALT Lymphoma Pretreated With Prior Systemic Therapy

Phase II Study of VELCADE in Patients With Extranodal Marginal Zone B-cell Lymphoma of MALT-type Pretreated With Prior Systemic Therapy Regimen (X05142)

The primary objective of this study is to assess the antitumor activity (in terms of overall response rate - ORR - i.e. sum of complete and partial responses)of bortezomib in pretreated MALT lymphomas with one prior sistemic therapy regimen

Inclusion Criteria:

1. histologically proven d MALT lymphoma at any extranodal site

2. any stage (Ann Arbor I-IV)

3. relapsed or refractory disease pretreated with prior chemotherapy regimens +/- anti-CD20 immunotherapy or prior anti-CD20 immunotherapy (any number of prior lines of therapy)

4. no evidence of histologic transformation to a high grade lymphoma

5. measurable or evaluable disease

6. age > 18 years

7. full recovery from previous therapy, with life expectancy of at least 6 months

8. ECOG performance status 0-2

9. for primary gastric localized H. pylori-positive disease at diagnosis:

   1. persistent disease 1 year after documented H. pylori infection eradication
   2. clinical, endoscopic (or histologic) evidence of progression at any time after H. pylori infection eradication

10. no prior chemotherapy, immunotherapy or radiotherapy in the last 6 weeks

11. no corticosteroids during the last 4 weeks, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms

12. adequate renal function (calculated or measured creatinine clearance >30 mL/minute), liver function (ASAT/ALAT <2,5 upper normal, total bilirubin <2,5x upper normal) and bone marrow function

13. no evidence of active opportunistic infections

14. no known HIV infection

15. no active HBV and/or HCV infection

16. no serious medical illness likely to interfere with participation in this clinical study

17. voluntary written informed consent before performance of any study-related procedure

18. female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study

Exclusion Criteria:

1. prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1(CIN1) or localized non-melanomatous skin cancer
2. other investigational drugs within 14 days before enrollment
3. evidence of symptomatic central nervous system (CNS) disease
4. severe impairment of bone marrow function (ANC <1.0x109/L, PLT <30x109/L within 14 days before enrollment), unless due to lymphoma involvement
5. evidence of ≥ grade 2 peripheral neuropathy within 14 days before enrollment
6. known hypersensitivity to bortezomib, boron or mannitol
7. pregnant or lactating status, confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
8. any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial