Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: dasatinib; Rituximab; fludarabine
Intervention description: Taken orally once a day on days 1-14 of each 28-day cycle; Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).; Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
Intervention MeSH terms: Rituximab; Fludarabine; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CLL; fludarabine; rituximab; dasatinib; refractory; relapsed

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.
    

Eligibility 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.