Study Evaluating the Safety and Efficacy of iR2 in Untreated and Unfit Elderly Patients With DLBCL

Study Overview
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Brief Summary
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This is a single-arm, open-label phase 2 study of iR2 in the treatment of unfit and elderly patients with untreated diffuse large B-cell lymphoma。

Detailed Description
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This open-label, single arm study will evaluate the efficacy and safety of ibrutinib， lenalidomide, rituximab (iR2) in previously untreated and unfit elderly subjects with diffuse large B-cell lymphoma. Subjects will receive 6 cycles of ibrutinib 560mg, day 1-21, orally (PO) , lenalidomide 25mg, day 1-10, rituximab 375mg/m2, intravenously, every 21 days.

Official Title
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A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of iR2 (Ibrutinib，Lenalidomide, Rituximab）in Untreated and Unfit Elderly Patients With Diffuse Large B-cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Ibrutinib
* Drug: Lenalidomide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed diffuse large B cell lymphoma, treatment naive Age > 75 years Ineligible for standard chemotherapy Must has measurable lesion in CT or PET-CT prior to treatment At least 3 months life expectation Informed consented No previous use of study drug Exclusion Criteria: Has accepted Chemotherapy before Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<80*10^9/L; ALT or AST >2*ULN; AKP or bilirubin >1.5*ULN ;Creatinine>1.5*ULN Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation HIV infection If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA,DNA positive patients cannot be enrolled. Other uncontrollable medical condition that may that may interfere the participation of the study

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iR2<br>Participants received six 21-day cycles of ibrutinib, lenalidomide, and rituximab (iR2) treatment (21-day cycles). | Drug: Ibrutinib<br>* Ibrutinib 560mg per day administered orally on Day 1-21 of each 21-day cycle for 6 cycles<br>* Other names: Imbruvica;Drug: Lenalidomide<br>* Lenalidomide 25mg per day administered orally on Day 1-10 of each 21-day cycle for 6 cycles<br>* Other names: Relvimid;Drug: Rituximab<br>* Rituximab 375mg/m2 per day administered intraveneously on Day 1 of each 21-day cycle for 6 cycles<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 6 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of participants with response(complete response and partial response) was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 6 (each cycle is 21 days) | 
| Progression free survival | Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first. | Baseline up to data cut-off (up to approximately 4 years) | 
| Overall survival | Overall survival in the overall study population was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. | Baseline up to data cut-off (up to approximately 4 years) | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Baseline up to data cut-off (up to approximately 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iR2