This phase II trial studies how well ibrutinib and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back or has not responded to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Giving ibrutinib and nivolumab may work better in treating patients with classical Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To estimate the complete response (CR) rate with ibrutinib at the standard dose of 560 mg daily in combination with nivolumab 3 mg/kg intravenously (IV) every 3 weeks up to 16 infusions in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) with ibrutinib and nivolumab in combination in patients with relapsed or refractory classical HL. II. To determine safety and toxicity of ibrutinib in combination with nivolumab in patients with relapsed or refractory cHL. III. To determine the progression free survival (PFS) in patients with relapsed or refractory cHL treated with combined ibrutinib and nivolumab. IV. To determine the duration of response in patients with relapsed or refractory cHL treated with ibrutinib in combination with nivolumab. TERTIARY OBJECTIVES: I. To determine the effects of ibrutinib and nivolumab on the distribution of T-, B-, and NK cells in the peripheral blood. II. To determine the effects of ibrutinib and nivolumab on Th1/Th2 cytokines profile and correlate this with treatment response. III. To determine the effects of ibrutinib and nivolumab on Th1/Th2 ration and specific IgG sub-isotypes. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 and nivolumab IV continuously over 60 minutes on day 1.Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Winship Cancer Center of Emory University
Atlanta, Georgia, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Proportion of patients in CR
Simon's two-stage design will be used to test the null hypothesis that the true CR rate is =\< 20% versus the alternative hypothesis that the true CR rate is \>= 50%.
Time frame: Up to course 7 (147 days)
Duration of response
Kaplan-Meier methods will be used to estimate duration of response curves and corresponding quantiles (including the median).
Time frame: From the first documentation of response (CR, partial response) to the first documentation of definitive disease progression or death from any cause, whichever occurs first, assessed up to 3 years
Incidence of adverse events measured by Common Terminology Criteria for Adverse Events version 4.03
Will be summarized by type and grade, including incidence of grade 3+ adverse events. Initially, adverse event data will be summarized regardless of attribution, but may also be summarized for treatment-related adverse events. Number of cycles administered and reasons for treatment discontinuation will also be summarized to assess tolerability.
Time frame: Up to 3 years
ORR
Defined as the number of patients who achieve a complete or partial remission divided by the number of evaluable patients, will be calculated with an exact 90% confidence interval.
Time frame: Up to 3 years
PFS
Kaplan-Meier methods will be used to estimate the PFS curves and corresponding quantiles (including the median).
Time frame: From the date of enrollment until the first documentation of objective disease progression or death from any cause, whichever occurs first, assessed up to 3 years
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