This phase II trial studies how well blinatumomab works in treating patients with Richter transformation. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of tumor cells to grow and spread. The goal of this trial is to learn if blinatumomab, when combined with ibrutinib and nivolumab, can help to control Richter transformation (RT, a type of blood cancer).
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03121534.
PRIMARY OBJECTIVE:
I. Determine the overall response rate (complete remission plus partial remission) in Richter’s transformation (RT) after 2 courses of blinatumomab, ibrutinib and nivolumab treatment.
SECONDARY OBJECTIVES:
I. Assess the safety and feasibility of administering blinatumomab combined with ibrutinib and nivolumab to patients with RT.
II. Determine the complete remission rate for RT after 1 and 2 courses of therapy.
III. Determine the progression-free survival rate for RT at 1 year.
IV. Determine the overall survival rate for RT at 1 year.
V. Determine the proportion of patients who proceed to allogeneic stem cell transplantation as next treatment.
EXPLORATORY OBJECTIVE:
I. Pre- and post-treatment (progression) tumor biopsies for immunologic analysis, including immune checkpoint expression by tumor and by infiltrating T cells, flow cytometry and ribonucleic acid (RNA)-sequencing analysis (including the potential to perform single cell RNA-sequencing [seq]) or array-based analysis of immune cell subsets.
OUTLINE:
CYCLE 1: Patients receive ibrutinib orally (PO) once daily (QD), nivolumab intravenously (IV) over 30 minutes every 2 weeks, and blinatumomab via continuous intravenous infusion (CIVI) on days 15-43. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity.
CYCLE 2: Patients receive ibrutinib PO QD, nivolumab IV over 30 minutes every 2 weeks, and blinatumomab via CIVI on days 1-28 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients ibrutinib PO QD for 4 weeks, and nivolumab IV over 1 hour on day 1. Cycles repeats every 4 weeks for up to 36 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6-12 months.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorPhilip A Thompson
