Working… Menu
Help guide our efforts to modernize
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02200848
Recruitment Status : Terminated (Recruitment difficulties and toxicity)
First Posted : July 25, 2014
Last Update Posted : January 12, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Georgetown University

Tracking Information
First Submitted Date  ICMJE July 22, 2014
First Posted Date  ICMJE July 25, 2014
Last Update Posted Date January 12, 2018
Study Start Date  ICMJE April 2014
Actual Primary Completion Date March 27, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
Recommended Phase II dose [ Time Frame: 1year ]
The dose at which less than 2 of 6 patients experience a dose limiting toxicity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02200848 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • Safety [ Time Frame: 2 years ]
    adverse events, serious adverse events, adverse events leading to discontinuation, deaths
  • Antitumor efficacy [ Time Frame: 2 years ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase I Study of Lenalidomide, Rituximab and Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Official Title  ICMJE A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Intervention  ICMJE 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:
  • Ibrutinib
  • PCI-32765
  • NSC# 748645
  • Imbruvica
  • Lenalidomide
  • alpha-[3-aminophthalimido] glutarimide
  • Revlimid
  • CC-5013
  • NSC#703813
  • Rituximab
  • IDEC-C2B8
  • Rituxan
Study Arms  ICMJE 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.
Intervention: Drug: Lenalidomide, Ibrutinib, Rituximab
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 10, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2014)
Actual Study Completion Date  ICMJE August 1, 2017
Actual Primary Completion Date March 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02200848
Other Study ID Numbers  ICMJE NCI#9540
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Chaitra Ujjani, MD Georgetown Lombardi Comprehsnive Cancer Center
PRS Account Georgetown University
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP