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.

Inclusion Criteria:

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.

Exclusion criteria:

1. Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma g I-II-IIIa-IIIb, Primary Mediastinal Lymphoma
2. Age \> 65 years
3. Patients ineligible to high-dose chemotherapy
4. Performance status \> 2 according to ECOG scale if not due to lymphoma
5. Patient has known or suspected hypersensitivity or intolerance to Rituximab
6. Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
7. CNS disease (meningeal and/or brain involvement by lymphoma)
8. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
9. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
10. Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
11. Cardiac ejection fraction \< 50% (MUGA scan or echocardiography)
12. Creatinine clearance \< 45 ml/min
13. Presence of major neurological disorders
14. HIV positivity, HCV positivity, HBV positivity with the exception of patients with HBcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
15. Active opportunistic infection
16. Major surgical intervention prior 3 months to randomization if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
17. Prior malignancies other than lymphoma in the last 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
18. Life expectancy \< 6 months
19. Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
20. If female, the patient is pregnant or breast-feeding.