Phase II Randomized Study With R-DHAP +/- Bortezomib as Induction Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Patients Eligible to Transplantation. BR-DHAP Versus R-DHAP.

1. Age 18-65

2. Relapsed/refractory disease after receiving one line of standard chemoimmunotherapy (R-CHOP, GA-CHOP, R-CHOP like)

3. Diffuse Large B-cell Lymphoma at relapse. Patient has to be re-biopsied prior to study entry. If this is harmful for the patient, the patient can be enrolled if archivial tumor sample and block from first diagnosis are available.

4. No prior Bortezomib therapy

5. Measurable and/or evaluable disease

6. Any Ann Arbor stage and IPI group at relapse

7. Performance status \< 2 according to ECOG scale unless due to lymphoma

8. No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)

9. Adequate hematological counts: ANC \> 1.5 x 109/L, Hgb \> 9 g/dl (transfusion independent), Platelet count \> 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement

10. HIV negativity, HCV negativity, HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)

11. Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total \< 2 x ULN) if not related to lymphoma

12. Normal kidney function (creatinine clearance \> 45 ml/min)

13. Cardiac ejection fraction \> 50% (MUGA scan or echocardiography)

14. Normal lung function

15. Absence of active opportunistic infections

16. Non peripheral neuropathy or active neurological non neoplastic disease of CNS

17. Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or no other disease life-threatening that can compromise chemotherapy treatment

18. Disease free of prior malignancies other than lymphoma for \> 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast

19. Life expectancy \> 6 months

20. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent

21. Written informed consent

22. Women must be:

* postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)

* surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),

* abstinent (at the discretion of the investigator/per local regulations), or

* if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 12 months after terminating treatment.

23. Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening

24. Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.

What this study is about