Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of LR-CHOP21 for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma
Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of LR-CHOP21 for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma
This is a prospective multicenter phase II pilot trial designed with the purpose of dose
 finding to evaluate the efficacy and safety of treatment with Lenalidomide plus R-CHOP21
 (LR-CHOP21) for elderly patients with untreated Diffuse Large B Cell Lymphoma (DLBCL).
Inclusion Criteria:

 1. Understand and voluntarily sign an informed consent form

 2. Able to adhere to the study visit schedule and other protocol requirements

 3. Histologic subtypes as follows:

 -  CD20 positive Diffuse large B-Cell lymphoma

 -  CD20 positive Follicular grade IIIb

 4. Age 60-80

 5. Untreated patients. In patients with bulky mass or systemic symptoms or compressive
 disease or rapidly progressive adenopathies a pre-study treatment is allowed with
 steroids and/or a single dose of Vincristine 1.4 mg/mq (max 2) in the seven days prior
 the start of the study treatment

 6. Measurable and/or evaluable disease

 7. Ann Arbor stage II, III, IV

 8. International Prognostic Index at low-intermediate, intermediate-high, high risk
 (2/3/4-5)

 9. Adequate haematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L
 unless due to bone marrow involvement

 10. Conjugated bilirubin up to 2 x UNL

 11. Alkaline phosphatase and transaminases up to 2 x UNL

 12. Creatinine clearance > 50 ml/min

 13. HIV negativity

 14. HCV negativity

 15. HBV negativity or patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative

 16. Cardiac ejection fraction (MUGA scan or echocardiography) > 45%

 17. Non peripheral neuropathy or CNS disease. Non testicular Lymphoma

 18. Life expectancy > 6 months

 19. Performance status < 2 according to ECOG scale

 20. Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing absence of
 any impairment in activity of daily living (ADL), of any condition defining a
 geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3
 comorbidities according to CIRS-G scale

 21. Disease free of prior malignancies for ≥ 3 years with exception of currently treated
 basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
 or breast

 22. Females of childbearing potential (FCBP) must agree to use two reliable forms of
 contraception simultaneously or to practice complete abstinence from heterosexual
 intercourse during the following time periods related to this study: for at least 28
 days before starting study drug;while participating in the study; for at least 28 days
 after discontinuation from the study

 -  The two methods of reliable contraception must include one highly effective
 method (i.e., intrauterine device (IUD), hormonal [birth control pills,
 injections, or implants], tubal ligation, partner's vasectomy) and one additional
 effective (barrier) method (i.e., latex condom, diaphragm, cervical cap)

 -  FCBP must be referred to a qualified provider of contraceptive methods if needed

 Exclusion Criteria:

 1. Lymphoblastic Lymphoma

 2. Burkitt Lymphoma

 3. Non Hodgkin lymphoma CD 20 negative

 4. Mantle Cell Lymphoma

 5. Follicular Non Hodgkin Lymphoma grade I-II-IIIa

 6. Primitive mediastinal diffuse large B cell lymphoma with only mediastinal involvement

 7. International Prognostic Index at low risk (1)

 8. Has known or suspected hypersensitivity or intolerance to Rituximab

 9. History of evolutive malignancy within the last 3 years other than squamous cell and
 basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast

 10. Extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy
 before enrollment within 3 years before the start of treatment

 11. Exposure to Rituximab prior to study entry

 12. 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 study

 13. CNS disease (meningeal and/or brain involvement by lymphoma) or Testicular involvement

 14. DVT in the last year

 15. History of clinically relevant liver or renal insufficiency; significant cardiac,
 vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic,
 hematologic, psychiatric, or metabolic disturbances

 16. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable
 dose for at least 3 months before first dose of study drug

 17. 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

 18. Creatinine clearance < 50 ml/min

 19. Presence of major neurological disorders

 20. HIV positivity

 21. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with
 HBV-DNA negative

 22. HCV positivity

 23. Active opportunistic infection

 24. Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing presence
 of any impairment in activity of daily living (ADL), of any condition defining a
 geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3
 comorbidities according to CIRS-G scale

 25. Any other co-existing medical or psychological condition that would preclude
 participation in the study or compromise ability to give informed consent