Phase I Study of Lenalidomide, Rituximab and Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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This study is for subjects diagnosed with recurrent or relapsed CLL/SLL. The purpose of this study is to test the safety of the combination of the drugs lenalidomide and ibrutinib at different dose levels, in combination with the drug rituximab. We want to find out what effects, good and/or bad, they have on patients with CLL/SLL. The hypothesis of the study is that it will be safe to give the three drugs in combination and the information learned from this trial will be used to study the 3 drug combination is a larger future trial.

Detailed Description
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Treatment consists of dose escalations of lenalidomide and ibrutinib and fixed doses of rituximab. A small expansion cohort to include 10 patients will follow once the recommended phase II dose is found.

Official Title
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A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Lenalidomide, Ibrutinib, Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma that requires treatment No prior systemic treatment within 4 weeks of enrollment No corticosteroids within 2 weeks prior to study entry Measurable disease must be present No concomitant anti-cancer therapies ECOG status </= 2 Patients with HIV infection are eligible Patients with treated CLL or SLL in CNS are eligible Non-pregnant and non-nursing Life expectancy greater than 60 days Adequate bone marrow, kidney and liver function No major surgery within 28 days or minor surgery within 5 days of starting treatment Exclusion Criteria: History od Richter's transformation History of prior allogeneic transplant Radioimmunotherapy within 1 year of enrollment Prior Bruton's tyrosine kinase inhibitor or lenalidomide History of allergic reactions to compounds similar to ibrutinib, lenalidomide or rituximab or hypersensitivity active or uncontrolled autoimmune hemolytic anemia or ITP Transfusion-dependent thrombocytopenia or bleeding disorders Active hepatitis B or C infections History of known Human Anti-Chimeric Antibody positivity History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome History of uncontrolled seizures Autoimmune disorder that requires active immunosuppression Stroke or intracranial hemorrhage within last 6 months History of congestive heart failure, myocardial infarction, unstable angina, uncontrolled arrhythmia or any Class 3 or 4 heart disease in the last 6 months No prior malignancy except if treated with curative intent with no active disease for more than 3 years; adequately treated non-melanoma skin cancer or cervical cancer in situ using warfarin or similar Vitamin K antagonists Unable to swallow capsules or disease significantly affecting gastrointestinal function or inhibiting small intestine absorption

Ages Eligible for Study
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Minimum Age: 18 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: Lenalidomide, Ibrutinib, Rituximab<br>Rituximab on day 1, lenalidomide days 1-21 and ibrutinib continuously for 6 cycles or until disease progression or intolerance to the combination. Single agent ibrutinib will then be continued until disease progression or intolerance. | Drug: Lenalidomide, Ibrutinib, Rituximab<br>* Dose level -2 Ibrutinib 280 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level -1 Ibrutinib 420 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level 1 Ibrutinib 420 mg; Lenalidomide 5 mg; Rituximab 375 mg/m2 Level 2 Ibrutinib 420 mg; Lenalidomide 10 mg; Rituximab 375 mg/m2 Level 3 Ibrutinib 420 mg; Lenalidomide 15 mg; Rituximab 375 mg/m2<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Phase II dose | The dose at which less than 2 of 6 patients experience a dose limiting toxicity | 1year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | adverse events, serious adverse events, adverse events leading to discontinuation, deaths | 2 years | 
| Antitumor efficacy | Proportion of patients who achieve stable disease, partial or complete response; progression-free survival defined as duration of time from start of treatment to time of progression or death | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenalidomide, Ibrutinib, Rituximab, CLL, SLL