Dasatinib for the Treatment of Waldenstrom Macroglobulinemia in Patients Progressing on Ibrutinib

Inclusion Criteria

• Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia
• Known tumor expression of mutated MYD88 performed by a Clinical Laboratory Improvement Act (CLIA) certified laboratory
• 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. 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
• Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum serum IgM level of > 2 times the upper limit normal
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• 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
• Absolute neutrophil count >= 500/ uL (growth factor not permitted) (within 30 days prior to cycle 1 day 1)
• Platelets >= 50,000/ uL (platelet transfusion not permitted) (within 30 days prior to cycle 1 day 1)
• Hemoglobin >= 7 g/dL (red blood cell [RBC] transfusion permitted) (within 30 days prior to cycle 1 day 1)
• Total bilirubin =< 2 mg/dL (within 30 days prior to cycle 1 day 1)
• Potassium >= lower limit of normal (LLN) (within 30 days prior to cycle 1 day 1)
• Magnesium >= LLN (within 30 days prior to cycle 1 day 1)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT [serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (within 30 days prior to cycle 1 day 1)
• Estimated glomerular filtration rate (GFR) >= 30 ml/min (within 30 days prior to cycle 1 day 1)
• 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

• Lactating or pregnant women
• Participants who are receiving any other investigational agents
• Prior therapy with BCR-ABL inhibitors
• Known central nervous system (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 corrected QT (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