Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

Inclusion Criteria

• Phase I portion of the study: Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL according to National Cancer Institute (NCI)-Working Group (WG) 1996 guidelines
• Phase I portion of the study: The following types of NHL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO):
• Mantle cell lymphoma (MCL)
• Follicular lymphoma (FL) - grades 1-3a
• Lymphoplasmacytic lymphoma (LPL)
• Marginal zone lymphoma (MZL)
• CLL in Richter's transformation
• B-cell prolymphocytic leukemia
• Phase I portion of the study: Patients with histologically confirmed classical hairy cell leukemia (HCL)
• Phase II portion of the study - histologically or flow cytometry confirmed diagnosis of BCLL/SLL according to NCI-WG 1996 guidelines; patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma
• Patients underwent >= 1 prior chemotherapy-based or immunotherapy-based regimen or targeted therapy (e.g., inhibitors of BTK, PI3K etc.) administered for >= 2 cycles, and have had either documented disease progression or no response (stable disease) to the most recent treatment regimen
• Patients with CLL/SLL must demonstrate active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment:
• A minimum of any one of the following constitutional symptoms:
• Unintentional weight loss > 10% within the previous 6 months prior to screening
• Extreme fatigue (unable to work or perform usual activities)
• Fevers of greater than 100.5 Fahrenheit (F) for >= 2 weeks without evidence of infection
• Night sweats without evidence of infection
• Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia
• Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly
• Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy
• Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months
• Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
• Patients with HCL must be intolerant of or not candidates for purine analog-based therapy, or failed to achieve response (CR or partial response [PR]) or relapsed within 2 years of such therapy, AND meet the standard treatment initiation criteria (absolute neutrophil count [ANC] = = 1 lesion that measures >= 2.0 cm in the longest dimension [LD] and >= 1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT] or magnetic resonance imaging [MRI]); for LPL, measurable disease will be defined as serum monoclonal IgM > 0.5 g/dL or meeting at least 1 of the recommendations from the Second International Workshop on LPL for requiring treatment
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status = = 50 mL/min
• Platelets >= 50, 000/mm^3 independent of transfusion support, with no active bleeding
• Absolute neutrophil count (ANC) >= 1000/mm^3, unless due to disease involvement in the bone marrow
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior therapeutic intervention with any of the following:
• Therapeutic anticancer antibodies within 4 weeks (rituximab), except within 6 months for obinutuzumab or a similar investigational type II monoclonal antibody;
• Radio- or toxin-immunoconjugates within 10 weeks;
• Inhibitors of BTK (ibrutinib), PI-3K (idelalisib), BH3-mimetic venetoclax, lenalidomide and other "targeted" therapy (including but not limited to investigational BTK and PI-3K inhibitors, etc.) - within 6 half-lives (i.e., 36 hours for ibrutinib)
• All other chemotherapy, radiation therapy