A Phase II Study of the FIL on Elderly Frail Patients With DLBCL

A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma.

This is a prospective, multicenter, single arm, phase II trial in elderly patients (≥ 70 years) affected by DLBCL defined as frail according to CGA and previously untreated.

The primary endpoint is to evaluate the efficacy of the R2 (Revlimid+Rituximab) combination in first line DLBCL patients not candidate for the standard R-CHOP (or R-CHOP like) treatments due to the frail status.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
2. Age ≥ 70 years
3. Previously untreated
4. CGA assessment performed before starting treatment
5. FRAIL patients defined as follows

   Age \> 80 years (with UNFIT profile):

   ADL ≥ 5 residual functions and/or IADL ≥ 6 residual functions and/or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2

   Age \< 80 (ONLY one of the following criteria):

   ADL ≤ 4 residual functions IADL ≤ 5 residual functions CIRS: 1 comorbidity of grade 3-4 or \> 8 comorbidities of grade 2
6. Ann Arbor Stage I - IV (Appendix F)
7. At least one bi-dimensionally measurable lesion defined as \> 1.5 cm in its largest dimension on CT scan
8. ECOG performance status of 0- 3 (Appendix E)
9. No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
10. Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:

    * Hemoglobin \> 10 g/dL
    * WBC \> 2500/mmc with PMN \> 1000/ mmc
    * Platelets count ≥ 75000/mmc
    * Creatinine clearance ≥ 10 mL/min
11. Ability and willingness to comply with the study protocol procedure
12. Life expectancy \> 6 months
13. Patients must give written informed consent.
14. Male subjects must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

1. Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
2. Previous exposure to cytotoxic agents
3. Suspect or clinical evidence of CNS involvement by lymphoma
4. Contraindication to the use of Rituximab or of Lenalidomide
5. HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided.
6. HIV positivity
7. Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
8. Any history of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
9. AST /ALT \> 2 x UNL; bilirubin \> 2 x UNL; serum creatinine \> 2.5 mg /dL
10. Creatinine clearance \< 10 mL/min
11. Evidence of any severe active acute or chronic infection
12. Severe cardiac dysfunction (NYHA grade III-IV)
13. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
14. Absence of caregivers in non-autonomous patients