This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib in treating patients with B-cell non-Hodgkin lymphoma that has returned (relapsed) or not responded to treatment (refractory). Lenalidomide helps shrink or slow the growth of non-Hodgkin lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide with ibrutinib may work better in treating non-Hodgkin lymphoma than giving either drug alone.
PRIMARY OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of lenalidomide and ibrutinib in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma (NHL). II. To define the qualitative and quantitative toxicities of the combination of lenalidomide and ibrutinib. SECONDARY OBJECTIVES: I. To describe the overall objective response rate to the combination of lenalidomide and ibrutinib in patients with relapsed or refractory B-cell NHL. II. To describe the response duration and two-year progression free survival (PFS) in patients with B-cell NHL receiving lenalidomide and ibrutinib. III. To characterize the pharmacokinetics of the combination of lenalidomide and ibrutinib in patients with relapsed or refractory B-cell NHL. IV. To identify associations of genetic polymorphisms in drug metabolizing enzymes, transporters or target genes with pharmacokinetics, pharmacodynamics, and clinical outcomes. V. To monitor the effects of combined therapy with ibrutinib and lenalidomide on B- T-, and natural killer (NK)-cell subsets by flow cytometry and quantitative immunoglobulin levels. VI. To explore the effects of the combination of ibrutinib and lenalidomide on pharmacodynamic markers including T helper cell, type 1 (TH1) and T helper cell, type 2 (TH2) cytokines, ex vivo NK cell cytotoxicity, serum micro ribonucleic acids (RNAs), plasma metabolites, and levels of Bruton's tyrosine kinase occupancy and other selected kinases. VII. To explore the relationship between pretreatment pathologic prognostic features and overall objective response. OUTLINE: This is a dose-escalation study. Patients receive lenalidomide orally (PO) on days 1-21 and ibrutinib PO on days 1-28 (days 2-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT or PET/CT throughout the study. Patients may undergo bone marrow biopsy and aspiration and MRI as clinically indicated. After completion of study treatment, patients are followed up for 4 weeks and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT and/or PET/CT
Given PO
Given PO
Undergo MRI
Undergo PET/CT
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Maximum tolerated dose (MTD)
Defined as the highest safely tolerated dose where at most one patient experiences dose limiting toxicity (DLT) with the next higher dose having at least 2 patients who experience DLT.
Time frame: 28 days
Incidence of toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria
Worst grade toxicities will be recorded for each patient and summarized using frequency tables. Tolerability of the regimen is assessed by summarizing the number of patients who required dose modifications and/or dose delays. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be counted.
Time frame: Up to 2 years
Number of patients responding to treatment
Responses will be summarized with simple descriptive statistics, delineating complete responses from lesser responses and stable disease or progressive disease according to the International Harmonization Project Lymphoma Response Criteria and the Response Criteria for Waldenstrom's Macroglobulinemia.
Time frame: Up to 2 years
Degree of response
Responses will be summarized with simple descriptive statistics, delineating complete responses from lesser responses and stable disease or progressive disease according to the International Harmonization Project Lymphoma Response Criteria and the Response Criteria for Waldenstrom's Macroglobulinemia.
Time frame: Up to 2 years
Duration of overall response
Summarized with simple descriptive statistics.
Time frame: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Duration of stable disease
Summarized with simple descriptive statistics.
Time frame: From the start of the treatment until the criteria for progression are met, assessed up to 2 years
Progression free survival (PFS)
Summarized with simple descriptive statistics.
Time frame: Duration of time from the start of treatment to the time of measured progression or death, assessed up to 2 years
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