This randomized phase II trial studies how well ibrutinib works when given together with vaccine therapies in treating patients without clinical signs or indications that raise the possibility of a particular disorder or dysfunction (asymptomatic) who have high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Vaccines, such as pneumococcal 13-valent conjugate vaccine, trivalent influenza vaccine, and diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed, may help the body build an effective immune response to kill cancer cells. Giving ibrutinib together with vaccine therapies may be a better treatment for chronic lymphocytic leukemia or small lymphocytic lymphoma.
PRIMARY OBJECTIVES: I. To determine the 2-year progression-free survival of asymptomatic, high-risk genomic chronic lymphocytic leukemia (CLL) patients treated with ibrutinib. SECONDARY OBJECTIVES: I. To determine whether concurrent administration of ibrutinib with 2 doses of the pneumococcal vaccine (pneumococcal 13-valent conjugate vaccine) does not negatively impact the immune response compared to those who receive the pneumococcal vaccination with sequential therapy. II. To determine the safety and toxicity associated with administering ibrutinib to asymptomatic, high-risk genomic CLL patients. III. To determine the response pattern (complete response \[CR\] minimal residual disease \[MRD\]-, CR, partial response \[PR\], PR with lymphocytosis, stable disease \[SD\]) in asymptomatic, genomic high-risk patients treated with ibrutinib. VI. To determine changes in the stress, anxiety and depressive symptoms, and related quality of life indicators from patients treated with ibrutinib.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Given IM
Given PO
Correlative studies
Correlative studies
Given IM
Ancillary studies
Given IM
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Proportion of patients who are alive and progression-free
Time frame: At 2 years from the date of the first ibrutinib administration
Degree of response (CR MRD-,CR, PR, PR with lymphocytosis, and SD)
Will be summarized across and within cohorts. Will graphically evaluate differences between responders and non-responders in select pharmacodynamic markers across and within arms using side-by-side boxplots. Provided an appropriate number of responses, will fit logistic regression models, with response as the dependent variable, and may find correlations of moderate significance that will merit further research in future studies. Time to treatment failure will be defined as the date of first ibrutinib therapy until the date of next treatment, date of death, or date off-study if due to toxicity, whichever occurs first, censoring patients at last follow-up. Response will be characterized according to a slight modification of the 2008 International Workshop on CLL (IWCLL) guidelines for the diagnosis and treatment of CLL, which include clinical, hematologic, and bone marrow features
Time frame: Up to 4 years
Incidence of adverse events, evaluated using the NCI CTCAE version 4.0
In general, the maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by and across arms to determine toxicity patterns. Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The incidence of severe (grade 3+) adverse events or toxicities will be described and reasons patients discontinue study treatment will be summarized.
Time frame: Up to 30 days after study treatment
Proportion of patients who achieve complete response
CR requires following for period of at least 2 months while during therapy: * Absence of adenopathy, hepatomegaly or splenomegaly on PE * Absence constitutional symptoms * Normal CBC as exhibited by polymorphonuclear leukocytes ≥ 1500/μL, PLT \> 100,000/μL, HGB \> 11.0 g/dL (untransfused), and lymphocyte count \< 4,000/ μL. Achieve clinical CR lasting for at least 2 months will undergo radiologic eval by CT scans of chest, abd and pelvis. Patients who have radiologic evidence of CR (including absence of lymphadenopathy \<1.5cm, absence of hepatomegaly and splenomegaly) will undergo bone marrow aspirate and biopsy * Bone marrow aspirate and biopsy must be normocellular for age with \<30% of nucleated cells being lymphocytes. Lymphoid nodules absent. Patients who fulfill criteria for CR with exception of having bone marrow lymphoid nodules will be considered a PR * 5 color flow cytometry will be used to characterize min. residual dis
Time frame: Within 2 years of starting ibrutinib treatment
Time to next treatment
Will be described across both cohorts by the Kaplan-Meier method.
Time frame: Date of first ibrutinib therapy until the date of next treatment, assessed up to 4 years
Time to treatment failure
Time to treatment failure will be defined as the date of first ibrutinib therapy until the date of next treatment, date of death, or date off-study if due to toxicity, whichever occurs first, censoring patients at last follow-up. Time to treatment failure will be described across both cohorts by the Kaplan-Meier method.
Time frame: Date of first ibrutinib therapy until the date of next treatment, date of death, or date off-study if due to toxicity, whichever occurs first, assessed up to 4 years
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