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

Trial Status: Active

This phase I trial studies the side effects of dasatinib for the treatment of Waldenstrom macroglobulinemia that is progressing on ibrutinib. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is a targeted therapy intended to treat your cancer by binding to the target protein called BTK. BTK is believed to be an important target for treatment of patients with specific gene mutations. Some patients who have disease progression after taking ibrutinib have these gene mutations. This study may help doctors assess the feasibility of using dasatinib as a possible treatment for Waldenstrom macroglobulinemia that is 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

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Contact: Jorge Julio Castillo
Phone: 617-632-4218
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Jorge Julio Castillo
Phone: 617-632-4218

PRIMARY OBJECTIVE:

I. To evaluate the toxicity profile of dasatinib in Waldenstrom macroglobulinemia (WM) patients who progressed on ibrutinib.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) of dasatinib in WM patients who are progressed on ibrutinib.

II. To evaluate the rate of complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD) to dasatinib in WM patients who progressed on ibrutinib.

III. To evaluate progression-free survival, time to next therapy (TTNT), and overall survival to dasatinib in WM patients who progressed on ibrutinib.

IV. To evaluate the impact of MYD88 and CXCR4 mutations on response to dasatinib in WM patients who progressed on ibrutinib.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jorge Julio Castillo

  • Primary ID 19-305
  • Secondary IDs NCI-2019-08023
  • Clinicaltrials.gov ID NCT04115059