Clinical Trial: Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Dose Escalation Study of Ibrutinib With Lenalidomide for Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Brief Summary: This phase I trial studies the side effects and best dose of lenalidomide when given together with ibrutinib in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has returned after a period of improvement or does not respond to treatment. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with ibrutinib may work better in treating chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To define the safety, tolerability and maximum tolerated dose (MTD) of lenalidomide when used in combination with ibrutinib in adults with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

SECONDARY OBJECTIVES:

I. To determine the response rate and response duration in relapsed and refractory CLL/SLL patients with ibrutinib and lenalidomide.

II. To characterize the plasma pharmacokinetic (PK) interaction between ibrutinib and lenalidomide.

III. To explore whether pharmacogenetic studies can predict response, resistance or toxicity to ibrutinib and lenalidomide.

IV. To explore the ability of ibrutinib to occupy its targets (Bruton's tyrosine kinase [BTK] in B-cells and interleukin-2 inducible kinase [ITK] in T-cells), and whether co-administration with lenalidomide influences this binding.

V. To explore the early and late immunologic consequences of combining ibrutinib with lenalidomide in relapsed and refractory CLL.

VI. To explore the impact of ibrutinib and lenalidomide on ras homolog family member H (RhoH) expression and whether baseline RhoH expression predicts outcomes with this regimen.

VII. To explore mechanisms of resistance to ibrutinib. VIII. To explore the influence of traditional and new CLL/SLL clinical and laboratory prognostic factors on response to ibrutinib and lenalidomide.

OUTLINE: This is a dose-escalation study of lenalidomide.

Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All patient safety information collected will be summarized using descriptive statistics (number of non-missing values, mean, median, standard deviation, minimum and maximum) for continuous variables and counts and percentages for categorical variables, where applicable.



Original Primary Outcome: MTD of lenalidomide when combined with ibrutinib defined as the highest dose in which less than or equal to 1/6 patients have dose limiting toxicity [ Time Frame: 28 days ]

Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patient safety information collected will be summarized using descriptive statistics (number of non-missing values, mean, median, standard deviation, minimum and maximum) for continuous variables and counts and percentages for categorical variables, where applicable.


Current Secondary Outcome:

  • Remission/response duration [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 90 days ]
    Response duration will be calculated, and the mean, median, minimum, and maximum values will be reported.
  • Response rates [ Time Frame: Up to 12 months ]
    Response rates will be calculated based on all the intention-to-treat subjects and reported along with its exact 95% confidence interval.


Original Secondary Outcome:

  • Response rates [ Time Frame: Up to 12 months ]
    Response rates will be calculated based on all the intention-to-treat subjects and reported along with its exact 95% confidence interval.
  • Remission/response duration [ Time Frame: From the time measurement criteria are met for complete remission (CR) or partial remission (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 90 days ]
    Response duration will be calculated, and the mean, median, minimum, and maximum values will be reported.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 24, 2013
Date Started: April 2013
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017