Trial on Lenalidomide Given as Maintenance Therapy for Relapsed Diffuse Large B Cell Lymphoma

A Phase II Trial to Evaluate the Safety and Activity of Single-agent Lenalidomide Given as Maintenance Therapy After Response to Second-line Therapy in Patients With Relapsed DLBCL, Not Eligible for High-dose Chemotherapy and ASCT (Autologous Stem-Cell Transplantation)

This phase II multi-institutional trial will explore the safety and efficacy of lenalidomide monotherapy given as maintenance therapy following salvage chemo-immunotherapy in patients with relapsed or refractory chemosensitive diffuse large B-cell lymphoma

Patients older than 65 years or younger but not eligible to high-dose chemotherapy and autologous stem cell transplantation with biopsy-proven diffuse large B-cell lymphoma relapsed to previous combination chemotherapy regimen ± rituximab, who achieved at least a partial response to second-line chemotherapy (ICE or DHAP/DHAOx ((D)examethasone (H)igh-dose (A)ra-C - cytarabine (P)latinol (cisplatin)) or MINE (Mesna Ifosfamide Mitoxantrone Etoposide) regimen) + rituximab will receive single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment until progression of disease. Dose reductions of study drug will be made in case of adverse events when reported as correlated and when clinically appropriate.

One-year progression free survival (PFS) will be the primary endpoint and overall survival, response rate and toxicity will be the secondary endpoints. With the null hypothesis (P0) of 1-year PFS of 30%, this study will consider a satisfactory efficacy of lenalidomide worth of further investigation a P1 corresponding to a 1-yr PFS of 50% (that is an absolute increase of 20% in terms of 1-yr progression-free survival). Considering a standard type I error (α) of 0,05 and a power of 80% (Type 2 error of 20%) 47 patients will be necessary for the trial.

Inclusion Criteria:

• Age > 65 years
• Age < 65 but not eligible to high-dose chemotherapy and autologous stem cell transplantation
• Biopsy-proven DLBCL relapsed to previous combination chemotherapy regimen ± rituximab
• PR (Partial Response) or CR (Complete Response) to second-line chemotherapy (ICE or DHAP/DHAOx or MINE regimen) + rituximab
• ECOG (Eastern Cooperative Oncology Group) performance status score < 4
• Female of childbearing potential (FCBP) must demonstrate to practice a proper contraception to avoid any pregnancy risk during the study and at least 28 days after the discontinuation of the study
• Male subjects must agree to practice a proper contraception during any sexual contact with females childbearing potential

Exclusion Criteria:

• CNS (Central Nervous System) involvement
• Prior ASCT
• TTP (Time To Progression) <6 months after first-line therapy
• Use of experimental drugs during second-line salvage chemotherapy
• Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus )
• Active infectious disease
• HIV, HBV (Hepatitis B Virus) or HCV (Hepatitis C Virus) - positivity
• Impaired liver function (Bilirubin >2 x upper normal limit; ALT (alanine aminotransferase) /AST (aspartate aminotransferase) /GGT (γ-glutamyltransferase) > 3 x upper normal limit) at one month from salvage chemotherapy conclusion
• Impaired renal function (creatinine clearance <50 ml/min) at one month from salvage chemotherapy conclusion
• Absolute neutrophil count (ANC) <1000/microL
• Platelet count <75.000 /mm3
• Hemoglobin <9 g/dL
• Non-co-operative behaviour or non-compliance
• Psychiatric diseases or conditions that might impair the ability to give informed consent
• Pregnant or lactating females