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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Lenalidomide, Ibrutinib, Rituximab

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Lenalidomide, Ibrutinib, Rituximab, CLL, SLL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Georgetown Lombardi Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide, Ibrutinib, Rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

Recommended Phase II dose

The dose at which less than 2 of 6 patients experience a dose limiting toxicity

Secondary Outcome Measures

Safety

adverse events, serious adverse events, adverse events leading to discontinuation, deaths

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

Full Information

NCT ID

NCT02200848

First Posted

July 22, 2014

Last Updated

January 10, 2018

Sponsor

Georgetown University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02200848

Brief Title

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

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Terminated

Why Stopped

Recruitment difficulties and toxicity

Study Start Date

April 2014 (undefined)

Primary Completion Date

March 27, 2017 (Actual)

Study Completion Date

August 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Georgetown University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Keywords

Lenalidomide, Ibrutinib, Rituximab, CLL, SLL

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lenalidomide, Ibrutinib, Rituximab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lenalidomide, Ibrutinib, Rituximab

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Recommended Phase II dose

Description

The dose at which less than 2 of 6 patients experience a dose limiting toxicity

Time Frame

1year

Secondary Outcome Measure Information:

Title

Safety

Description

adverse events, serious adverse events, adverse events leading to discontinuation, deaths

Time Frame

2 years

Title

Antitumor efficacy

Description

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

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chaitra Ujjani, MD

Organizational Affiliation

Georgetown Lombardi Comprehsnive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Georgetown Lombardi Comprehensive Cancer Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

29610115

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.

Results Reference

derived

Learn more about this trial

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

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