A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (greater than or equal to 70 Years of Age) With Chronic Lymphocytic Leukemia (CLL).

This phase III trial studies how well ibrutinib and obinutuzumab with or without venetoclax works in treating older patients with untreated chronic lymphocytic leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as venetoclax work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia.

Key Eligibility

• Patients must have been diagnosed with chronic lymphocytic leukemia (CLL) and have greater than 5000 B-cells per uL of peripheral blood at any point during the course of their disease
• This blood submission is mandatory prior to registration/randomization to perform fluorescence in situ hybridization (FISH) centrally that will be used for stratification. It should be obtained as soon after pre-registration as possible
• Patients must be diagnosed with CLL in accordance with 2018 IWCLL criteria that includes all of the following:
◦ Greater than or equal to 5 x10^9 B lymphocytes (5000/uL) in the peripheral blood measured by flow cytometry at any point in the course of the disease
◦ On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
◦ CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics
• Patients must be intermediate or high-risk Rai stage CLL.
◦ Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly
◦ High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia
• Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
Phase III
Alison Conlin, M.D.
Neysa Dagostino

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.