A Phase II Multicenter Non-randomized Study to Assess Safety, Toxicity and Clinical Activity of the Association of Bortezomib(VELCADE)With Rituximab in Relapsed/Refractory Indolent Non Follicular and Mantle-cell Non-Hodgkin Lymphoma
1. Patients with naïve or sensitive rituximab indolent non-follicular and mantle cell
non-Hodgkin's Lymphoma disease that had failed to respond or relapsed after primary
therapy. There is a demonstrated progressive disease requiring further treatment.
Histological subtype included into the study are are as follows Small
lymphocytic/lymphoplasmocytic lymphoma; Nodal marginal zone Lymphoma (MALT lymphoma
are excluded) Splenic marginal zone lymphoma Mantle cell lymphoma A lymphnode biopsy
is advisable if it is not harmful for the patients, before enrollment of the patient
into the study in order to confirm diagnosis and to rule out histologic
transformation. Lymphnode biopsy should be performed within 6 months before study
2. Age >18-75
3. Relapse or failure to respond after one or more (maximum three) lines of chemotherapy
4. Any type of prior chemotherapy, rituximab included. Patients who had received high
dose chemotherapy and ASCT can be enrolled into the study
5. Naïve or sensitive rituximab disease. If the patient received Rituximab, he/she must
have responded and the TTP from the last dose to rituximab must have been 6 months or
6. Measurable and/or evaluable disease.
7. Adequate haematological counts: ANC> 1.0 x 109/L and PLT counts> 75 x 109/L unless
due to bone marrow involvement by lymphoma.
8. Conjugated bilirubin up to 2 x ULN.
9. Alkaline phosphatase and transaminases up to 2 x ULN.
10. Creatinine clearances> 30 m/min.
11. Non peripheral neuropathy or CNS disease.
12. Life expectancy> 6 months.
13. Performance status< 2 according to ECOG scale.
14. Written informed Consent
1. Has known or suspected hypersensitivity or intolerance to rituximab, boron, mannitol,
or heparin, if an indwelling catheter is used
2. History of clinically relevant liver or renal insufficiency; significant cardiac,
vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic,
hematologic, psychiatric, or metabolic disturbances
3. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable
dose for at least 3 months before first dose of study drug
4. Uncontrolled or severe cardiovascular disease including myocardial infarction within
6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart
failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina,
clinically significant pericardial disease, or cardiac amyloidosis
5. History of hypotension or has decreased blood pressure (sitting systolic blood
pressure SBP 100 mmHg and/or sitting diastolic blood pressure DBP 60 mmHg)
6. Pregnant or breastfeeding
7. Peripheral Neuropathy or Neuropathic Pain Grade 2
8. HIV positivity
9. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with
10. HCV positivity with the exception of patients with no signs of active chronic
hepatitis histologically confirmed
11. Active opportunistic infection
12. Receipt of extensive radiation therapy, systemic chemotherapy, or other
antineoplastic therapy within 4 weeks before enrollment
13. Exposure to Rituximab within 24 weeks before screening
14. Have 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
15. Any other co-existing medical or psychological condition that would preclude
participation in the study or compromise ability to give informed consent