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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Lenalidomide, Ibrutinib, Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Chaitra Ujjani, MD, Georgetown Lombardi Comprehsnive Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): March 27, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Actual): January 12, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Rituximab; Lenalidomide; Ibrutinib; CLL; SLL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Synthesis Inhibitors; Lenalidomide; Rituximab; Glutarimide
• Other Study ID Numbers: NCI#9540