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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02200848
• Other study ID #: NCI#9540
• Status: Terminated
• Phase: Phase 1
• First received: July 22, 2014
• Last updated: January 10, 2018
• Start date: April 2014
• Est. completion date: August 1, 2017

Study information

• Verified date: May 2017
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 1, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

Intervention

Drug:
• Lenalidomide, Ibrutinib, Rituximab
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

Locations

Country	Name	City	State
United States	Georgetown Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase II dose	The dose at which less than 2 of 6 patients experience a dose limiting toxicity	1year
Secondary	Safety	adverse events, serious adverse events, adverse events leading to discontinuation, deaths	2 years
Secondary	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