Clinical trial NCT02200848: Phase I Study of Lenalidomide, Rituximab and Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Official title: A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: Lenalidomide
Ibrutinib
Rituximab
CLL
SLL
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-07-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recommended Phase II dose
timeFrame: 1year
Secondary outcomes:
measure: Safety
timeFrame: 2 years
measure: Antitumor efficacy
timeFrame: 2 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
Study officials:
affiliation: Georgetown Lombardi Comprehsnive Cancer Center
name: Chaitra Ujjani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ujjani C, Wang H, Skarbnik A, Trivedi N, Ramzi P, Khan N, Cheson BD. A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL. Blood Adv. 2018 Apr 10;2(7):762-768. doi: 10.1182/bloodadvances.2017015263.