Dasatinib In Waldenström Macroglobulinemia

Inclusion Criteria:

* Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1.
* Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia
* Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory.
* Participants must have a BTKCys481 and/or PLCγ2 mutation. Genomic alterations must be confirmed via sequencing performed at NeoGenomics Laboratories
* At least one previous therapy, with ibrutinib as the most recent treatment. Participants may remain on ibrutinib therapy during screening. A 1 day washout before starting dasatinib is required.
* Documented disease progression on last regimen (ibrutinib) per the Sixth International Workshop on WM. One or more of the following:
* 25% increase in serum IgM level with at least 500 mg/dL absolute increase from nadir with re-confirmation
* Progression of clinically significant disease related symptoms
* Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM \[26\]. One or more of the following:

  * Constitutional symptoms
  * Progressive or symptomatic lymphadenopathy or splenomegaly
  * Hemoglobin \<10 g/dL
  * Platelet count \<100 k/uL
  * Symptomatic peripheral neuropathy
  * Systemic amyloidosis
  * Renal insufficiency
  * Symptomatic cryoglobulinemia
* Age 18 years or older
* Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum serum IgM level of \> 2 times the upper limit normal.
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
* Women of childbearing potential: 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: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study. FCBP must be referred to a qualified provider of contraceptive methods if needed.
* Men must agree to use a latex condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy.
* Participants must have normal organ and marrow function as defined below:

  * Absolute neutrophil count ≥500/ uL (Growth factor not permitted)
  * Platelets ≥50,000/ uL (Platelet transfusion not permitted)
  * Hemoglobin ≥ 7 g/dL (RBC transfusion permitted)
  * Total bilirubin ≤ 2 mg/dL
  * Potassium ≥ LLN
  * Magnesium ≥ LLN
  * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  * Estimated GFR ≥ 30 ml/min
* Able to swallow pills.
* 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:

* Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
* Lactating or pregnant women.
* Participants who are receiving any other investigational agents.
* Prior therapy with BCR-ABL inhibitors.
* Known CNS lymphoma.
* Symptomatic hyperviscosity requiring urgent therapy.
* Human Immunodeficiency Virus (HIV), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pleural or pericardial effusion, unstable angina pectoris, cardiac arrhythmia, QT Prolongation, or psychiatric illness/social situations that would limit compliance with study requirements.
* Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
* History clinically significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes
* Known history of alcohol or drug abuse
* On any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin.
* History of non-compliance to medical regimens.
* Treatment with strong CYP3A4/5 inhibitors or inducers
* Participants who are taking St. Johns Wort. Must discontinue at least 5 days before starting dasatinib.
* Treatment with H2 Antagonists and proton pump inhibitors