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

Phase 2

Completed

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Lenalidomide

• Registration Number: NCT00799513
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2008-11-20
• Study First Submitted QC: 2008-11-28
• Study First Posted: 2008-12-01
• Study Start: 2009-03
• Primary Completion: 2017-03
• Study Completion: 2021-08
• Results First Submitted: 2023-11-29
• Results First Submitted QC: 2024-03-12
• Status Verified: 2024-04
• Results First Posted: 2024-04-09
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lenalidomide	Lenalidomide	single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment after the end of second-line chemotherapy until progression of disease.

Primary Outcome Measures

Name	Time	Method
1-year Progression-free Survival	1-year	It is defined as the number of participants alive after 1 year from enrolment to progression or relapse of lymphoma (if post-induction disease status was PR (Partial Response) or CR (Complete Response), respectively). Patients alive at last follow-up will be censored.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	5 years	Secondary measures to describe long term outcome of treatment; -Overall survival It is defined as the number of participants alive at 5ys from enrolment (death for any cause). Patients alive at last follow-up will be censored.
Progression Free Survival	5 years	Secondary measures to describe long term outcome of treatment; -Progression free survival It is defined as the number of participants, on a 5 yrs follow up, free from disease progression
Duration of Response	5 years	Secondary measures to describe long term outcome of treatment; * Duration of response It is defined as the number of participants experiencing a PFS (Progression Free Survival) from study therapy longer than previous line of treatment
Progression	5 years	Progression It is defined as the number of participants with disease recurrence observed on a 5 yrs follow up.

Trial Locations

Locations (1)

San Raffaele Scientific Institute; 🇮🇹 Milan, Italy