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

NCT ID: NCT02200848

Last Updated: 2018-01-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2017-08-01

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide, Ibrutinib, Rituximab

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.

Group Type: EXPERIMENTAL

Lenalidomide, Ibrutinib, Rituximab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Ibrutinib; PCI-32765; NSC# 748645; Imbruvica; Lenalidomide; alpha-[3-aminophthalimido] glutarimide; Revlimid; CC-5013; NSC#703813; Rituximab; IDEC-C2B8; Rituxan

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Georgetown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chaitra Ujjani, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown Lombardi Comprehsnive Cancer Center

Locations

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29610115 (View on PubMed)

Other Identifiers

NCI#9540

Identifier Type: -

Identifier Source: org_study_id