Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas

Inclusion Criteria:

• Men and women >= 18 years of age

• Patients will need to have one of the following clinical scenarios:

• Previously untreated follicular lymphoma grade 1-3a with low tumor burden byGroupe d'Etude des Lymphomes Folliculaires (GELF) criteria

• Previously untreated follicular lymphoma grade 1-3a with high tumor burden byGELF criteria but who are unable or unwilling to receive standard front-linetreatment approaches

• Previously untreated marginal zone lymphoma, lymphoplasmacytic lymphoma, or anyother indolent B-cell lymphoproliferative disorder with low tumor burden byGELF criteria or who are unable/unwilling to receive more intensive front-linetreatment

• Previously untreated mantle cell lymphoma who would otherwise be appropriatecandidates for watchful waiting OR who have symptomatic disease but are notcandidates for or decline standard induction approaches

• Patients with previously untreated low tumor burden FL (criterion above) must havemeasurable and/or assessable disease defined as at least one involved lymph node orextranodal disease site that measures >= 1.5cm in greatest diameter

• Patients who meet inclusion criteria above are eligible as long as they meet one ofthe following criteria for measurable/assessable disease:

• At least one involved lymph node or extranodal disease site measuring > 1.5cmin greatest diameter

• Pathologically-confirmed bone marrow or peripheral blood involvement that canbe reassessed for response

• Pathologically confirmed splenic or extranodal involvement with at least oneknown site of disease remaining after diagnostic biopsy that can be reassessed (i.e., patients with splenic marginal zone lymphoma who complete splenectomyand have no other detectable disease would not be eligible)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Woman of childbearing potential (WOCBP) and men enrolled on this protocol must agreeto use adequate contraception (hormonal or barrier method of birth control;abstinence) prior to study entry for the duration of study participation, and for atleast 2 days after the last dose of acalabrutinib or 18 months after the last doseof obinutuzumab, whichever is longer. Should a woman become pregnant or suspect sheis pregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately

• Women of childbearing potential must have a negative serum or urine pregnancy testprior to starting therapy

• Willing and able to participate in all required evaluations and procedures in thisstudy protocol

• Ability to understand the purpose and risks of the study and provide signed anddated informed consent and authorization to use protected health information Abilityto understand the purpose and risks of the study and provide signed and datedinformed consent and authorization to use protected health information

Exclusion Criteria:

• The presence or history of histologically transformed or co-existing high-grade oraggressive non-Hodgkin lymphoma

• Confirmed active or prior central nervous system disease

• Prior receipt of lymphoma-directed therapy or prior antibody-based therapy (exceptfor anti-microbial therapy for infection-associated marginal zone lymphoma such ashepatitis C or H pylori)

• A short course of steroids is permitted for patients aside from those in thelow tumor burden FL cohort. This course may be no more than 14 days andsteroids must be discontinued (or tapered to =< 10mg prednisone or equivalent)no later than 3 days after initiation of study treatment. Patients in the lowtumor burden FL cohort may not receive corticosteroids as an anti-lymphomatherapy at any time before starting treatment

• Prior malignancy (or any other malignancy requiring active treatment), except foradequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,or other cancer from which the subject has been disease free for >= 2 years or whichwill not limit survival to < 5 years

• Clinically significant cardiovascular disease such as symptomatic ventriculararrhythmias, congestive heart failure, or myocardial infarction within 6 months ofscreening, or any class 3 or 4 cardiac disease as defined by the New York HeartAssociation Functional Classification. Note: Subjects with controlled, asymptomaticatrial fibrillation can enroll on study if deemed appropriate by the investigator

• Has difficulty with or is unable to swallow oral medication, or has significantgastrointestinal disease that would limit absorption of oral medication

• Known history of human immunodeficiency (HIV) or any active significant infection (e.g., bacterial, viral, or fungal) within 14 days of cycle 1. Patients withuncomplicated viral or bacterial infections that are being managed with oralantibiotics and/or supportive care alone are eligible

• Known history of hypersensitivity or anaphylaxis to study drug(s) including activeproduct or excipient components

• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebranddisease)

• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenicpurpura)

• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months beforescreening

• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer

• Requires or receiving anticoagulation with warfarin or equivalent vitamin Kantagonists

• Requires treatment with proton pump inhibitors (e.g, omeprazole, esomeprazole,lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjectsreceiving proton pump inhibitors who switch to H2-receptor antagonists or antacidsare eligible for enrollment to this study

• History of significant cerebrovascular disease/event, including stroke orintracranial hemorrhage, within 6 months before the first dose of study drug.Patients with a transient ischemic attack which has resolved and for which there areno ongoing symptoms are eligible

• Major surgical procedure within 28 days of first dose of study drug (not including adiagnostic procedure to make the lymphoma diagnosis). Note: If a subject had majorsurgery, they must have recovered adequately from any toxicity and/or complicationsfrom the intervention before the first dose of study drug

• Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative willneed to have a negative polymerase chain reaction (PCR) and must be willing toundergo deoxyribonucleic acid (DNA) PCR testing during the study to be eligible.Those who are HBsAg positive or hepatitis B PCR positive will be excluded. Subjectswho are hepatitis C antibody positive will need to have a negative PCR result to beeligible and have completed appropriate anti-viral treatment. Those who arehepatitis C PCR positive will be excluded. Anti-viral therapy for patients withhepatitis-C associated marginal zone lymphoma will not be considered a prioranti-lymphoma treatment

• Absolute neutrophil count (ANC) < 1,000/mcL

• Platelet count < 50,000/mcL (Unless felt to be related to underlying disease)

• Total bilirubin >= 1.5 x the upper limit of normal (ULN). Isolated bilirubin > 1.5 xULN is permitted if the direct proportion is < 35%

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN

• Creatinine clearance =< 40 mL/min/1.73m^2

• Breastfeeding or pregnant

• Concurrent participation in another therapeutic clinical trial