Venetoclax With Obinutuzumab and Magrolimab (VENOM) in Relapsed and Refractory Indolent B-cell Malignancies

• INCLUSION CRITERIA:
• Patients must have a confirmed histologic diagnosis of an indolent cluster of differentiation 20 (CD20) positive B-cell lymphoma according to the criteria established by the 2016 version of the World Health Organization (WHO) classification system. Lymphomas with any prior CD20 expression (by immunohistochemistry or flow cytometry) will be considered eligible. Diagnosis must be confirmed by Laboratory of Pathology, National Cancer Institute (NCI) and the following indolent B-cell lymphomas are included:
• Follicular lymphoma (FL): must be grade 1-2 or 3a
• Marginal zone lymphoma (MZL)
• Mantle cell lymphoma (MCL)
• Chronic lymphocytic leukemia (CLL)
• Participant must have relapsed and/or refractory disease, as defined below:
• FL: relapsed after and/or refractory to at least two (2) prior lines of therapy with at least one of those therapies containing an anti-CD20 monoclonal antibody.

NOTE: Participants with FL may be eligible after one (1) prior line of therapy if they have either:

• Follicular lymphoma international prognostic index (FLIPI) >=2 (120)
• Disease progression within 24 months of the end of last therapy (POD24)
• MZL: relapsed after and/or refractory to at least two (2) prior lines of therapy, with at least one containing an anti-CD20 monoclonal antibody.
• MCL: relapsed after and/or refractory to at least two (2) prior lines of therapy, with at least one containing an anti-CD20 monoclonal antibody.

NOTE: Participants with MCL may be eligible after one (1) prior line of therapy if they have either:

• Blastoid or pleomorphic histology
• 17p deletion
• Tumor protein p53 (TP53) mutation or deletion
• Antigen Kiel 67 (Ki67) >=30%
• Received a Bruton tyrosine kinase (BTK) inhibitor as first line therapy
• CLL: relapsed after and/or refractory to at least two (2) prior lines of therapy. Participants with CLL are not required to have had therapy containing anti-CD20.

NOTE: Participants with CLL may be eligible after one (1) prior line of therapy if they have either:

• 17p deletion
• TP53 mutation or deletion
• Received both a Bruton's Tyrosine Kinase (BTK) inhibitor AND a B-cell lymphoma 2 (BCL2) inhibitor as first line therapy

NOTE: Participants must not have received prior treatment with a cluster of differentiation 47 (CD47) or signal regulatory protein (SIRP) targeting agent

-Adequate tissue from diagnostic biopsy (archival or fresh) must be available for performance of correlative studies

NOTE: Tumor tissue may be from any previously collected tissue and adequacy is at the discretion of the Principal Investigator. If prior tissue is not available, patient must be willing to undergo baseline tissue biopsy (for patients with known or suspected bone marrow involvement, bone marrow may be acceptable tissue per discretion of the investigator).

-Patients must have at least evaluable disease as assessed by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on computed tomography (CT) or magnetic resonance imaging (MRI) and/or evaluable fludeoxyglucose-18 (FDG)-avid lesions on positron emission tomography (PET). Patients may also have measurable disease.

NOTE: Patients with known active central nervous system (CNS) lymphoma are not eligible.

• Age greater than or equal to 18 years

NOTE: Because no dosing or adverse event data are currently available on the use of magrolimab in patients 1.5 X ULN, per discretion of the investigator

-The effects of the study drugs on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and for the following time frames after the last dose of drug, whichever i