This is Phase I pilot, single center study designed to explore the safety of Dasatinib in symptomatic Waldenström Macroglobulinemia participants who are progressing on ibrutinib therapy with BTK Cys481 or PLCG2 mutations
This research study is a Pilot Study, which is the first time investigators are examining this drug in patients with Waldenström Macroglobulinemia who have progressed on ibrutinib. Patients who fulfill eligibility criteria will be entered into the trial to receive Dasatinib After the screening procedures confirm participation in the research study: The participant will be given a study drug-dosing calendar for each treatment cycle. In this research study, the investigators are planning to give Dasatinib, which is a targeted therapy intended to treat 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. * Making treatment decisions based on genetic testing is investigational, and the FDA has not approved this genetic testing. The U.S. Food and Drug Administration (FDA) has not approved Dasatinib for Waldenström Macroglobulinemia but it has been approved for other uses. Dasatinib is produced by Bristol-Myers Squibb.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Oral, daily, dosing per protocol, once a day for cycle
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Number of Participants With at Least One Treatment-Emergent Adverse Event
Count of participants who experience a treatment-emergent adverse event
Time frame: 2 years
Overall Response Rate
Percentage of patients with an Overall Response. Overall Response Rate= Minor response (\>25%-50% reduction in serum IgM from baseline) + Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Time frame: 2 years
Complete Response Rate
Percentage of patients with Complete Response (CR). Complete Response requires resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, and resolution of any adenopathy or splenomegaly.
Time frame: 2 years
Very Good Partial Response Rate
Percentage of patients with very good partial response (VGPR) to therapy. (VGPR is \>90% reduction in serum IgM from baseline)
Time frame: 2 years
Partial Response Rate
Percentage of patients with partial response (PR) to therapy. (PR is 50-89% reduction in serum IgM from baseline)
Time frame: 2 years
Minimal Response Rate
Percentage of patients with Minor Responses to therapy. (MR is 25-49% reduction in serum IgM from baseline)
Time frame: 2 years
Stable Disease Rate
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Percentage of patients with Stable disease to therapy. (SD is \<25% reduction in serum IgM from baseline).
Time frame: 2 years
Progressive Disease Rate
Percentage of patients with who experienced disease progression on study. PD is \>25% increase in serum IgM from baseline with an absolute increase of at least 500 mg/dL, or progression of clinically significant disease related symptoms. Death from any cause or initiation of a new anti-neoplastic therapy will also be considered a progression event. An increase of 1 cm in any axis for adenopathy, or 2 cm in the craniocaudal axis of the spleen will be considered evidence of progression of extramedullary disease. Development of Bing Neel syndrome, or other extramedullary disease manifestations, as well as disease transformation will be considered as progressive events.
Time frame: From first dose through disease progression, up to 2 years from baseline
Progression Free Survival
The amount of time between starting treatment and experiencing disease progression. PD is \>25% increase in serum IgM from baseline with an absolute increase of at least 500 mg/dL, or progression of clinically significant disease related symptoms. Death from any cause or initiation of a new anti-neoplastic therapy will also be considered a progression event. An increase of 1 cm in any axis for adenopathy, or 2 cm in the craniocaudal axis of the spleen will be considered evidence of progression of extramedullary disease. Development of Bing Neel syndrome, or other extramedullary disease manifestations, as well as disease transformation will be considered as progressive events.
Time frame: From first dose through disease progression, up to 2 years from baseline
Time to Next Therapy (TTNT)
The amount of time between starting study treatment and initiating a new therapy
Time frame: From first dose through initiation of new therapy, up to 2 years from baseline
Overall Survival
The number of participants who are still alive at the end of follow-up. Participants were observed for up to 2 years after discontinuing study therapy for survival status.
Time frame: From first dose through death, up to 2 years from baseline