Inclusion Criteria:

• Clinicopathological diagnosis of Waldenström Macroglobulinemia (Owen et al. 2003), and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia (Kyle et al. 2003).
• Bone marrow at screening positive for CD38 expression by flow cytometry and/or immunohistochemistry.
• At least one previous treatment for WM with either documented disease progression or no response (stable disease) to the most recent treatment regimen.
• Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of >2 times the upper limit of normal of each institution is required.
• Participants with symptomatic hyperviscosity or serum IgM >5,000 mg/dL to undergo plasmapheresis prior to treatment initiation.
• Age ≥ 18 years old.
• ECOG performance status ≤ 2.
• Participants must have preserved organ and marrow function as defined below:
  • Absolute neutrophil count ≥ 1,000/mcL;
  • Platelets ≥ 50,000/mcL;
  • Hemoglobin ≥ 8 g/dL;
  • Total bilirubin ≤ 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease;
  • AST/ALT ≤ 2.5 × institutional upper limit of normal;
  • EGFR ≥ 30 ml/min;
  • Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin. Participants progressing on ibrutinib therapy (or other BTK inhibitor) may continue on therapy through screening, stopping at least 1 day prior to Cycle 1 Day 1.
• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study:
  • while participating in the study; and
  • for at least 90 days after discontinuation from the study. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test at screening.
• Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
• Able to adhere to the study visit schedule and other protocol requirements.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent study participation.
• Concurrent use of any other anti-cancer agents or treatments or any other investigational agents.
• Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Known CNS lymphoma.
• New York Heart Association classification III or IV heart failure.
• Known history of Human Immunodeficiency Virus (HIV).
• Active infection with Hepatitis B Virus (HBV) including participants with positive HBsAg testing at screening. Participants with evidence of resolved infection (i.e., who are HBsAg negative but positive for antibodies to Hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen (anti-HBs) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive are excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Active infection with Hepatitis C Virus (HCV) (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Lactating or pregnant women.
• Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy.
• History of non-compliance to medical regimens.