Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL

• Status: Terminated
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death of CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells. The purpose of this study is to see of the study drug dasatinib, in combination with fludarabine and rituximab, is safe and effective to use for people with relapsed or refractory CLL/SLL.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Bristol-Myers Squibb; Dana-Farber Cancer Institute
• Treatments: Dasatinib; Fludarabine; Fludarabine phosphate; Rituximab; Vidarabine

Criteria

Inclusion Criteria:

• CLL/SLL with cells positive by flow cytometry (or immunostaining) for CD19, CD23, and CD5. Patients may be CD23 negative as long as they are also cyclin D1 negative or t(11;14) negative.

• Participants must have received at least 1 prior regimen containing a purine analogue or have received at least 2 chemotherapy regimens not containing a purine analogue. Patients may be refractory to single-agent purine analogue treatment, but patients may not be refractory to a combination of purine analogue with rituximab. Patients may have received rituximab.

• 18 years of age or older

• Able to take oral medications

• ECOG Performance Status of 2 or better

• Adequate organ function to tolerate chemotherapy

• Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration and agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study is stopped.

• Require treatment based on 1996 NCI-WG criteria updated in 2008 by the IWCLL

• Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy and stop at least 5 days before starting dasatinib.

• Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib

Exclusion Criteria:

• Pregnant or breastfeeding women

• Uncontrolled angina, congestive heart failure, or MI within 6 months

• Diagnosed or suspected congenital long QT syndrome

• Any history of clinically significant ventricular arrhythmias

• Prolonged QTc interval on pre-entry ECG

• Uncontrolled hypertension

• Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration

• Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes

• Known HIV positive

• Known significant bleeding disorder unrelated to CLL

• Any significant pleural or pericardial effusion

• Patients may not have another malignancy that is uncontrolled or requires treatment within a year of starting this study.