A Study of Bafetinib as Treatment for Patients with Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Bafetinib is a dual protein kinase inhibitor, targeting both bcr/abl and Lyn kinases. B-cell chronic lymphocytic leukemia cells overexpress Lyn kinase compared to normal B lymphocytes as well as acute leukemias (ALL and AML), and inhibition of Lyn kinase induces apoptosis in cultures of B-CLL cells. Thus, bafetinib may stop the growth of B-CLL cells by inhibiting Lyn kinase, the molecule that couples the B cell receptor to downstream signaling.

Inclusion Criteria:

• Age ≥18 years, male or female.

• B-cell chronic lymphocytic leukemia meeting the WHO criteria.

• Relapsed or refractory disease with at least one of the following criteria: *progression after at least one course of a purine nucleoside analog (fludarabine phosphate, cladribine, pentostatin)

  • progression after at least one course of an alkylating agent (cyclophosphamide or chlorambucil)
  • relapse within 12 months after at least one course of either a purine nucleoside or an alkylating agent.

• Capable of providing informed consent and complying with trial procedures.

• ECOG performance status 0-2.

• Requires chemotherapy for disease as shown by any of the following criteria:

  • measurable and progressive lymphocytosis
  • measurable and progressive lymphadenopathy (lymph node ≥2 cm in a single diameter)
  • either weight loss ≥10% within the past 6 months or extreme fatigue due to leukemia
  • fevers ≥100.5 degrees F for 2 weeks with no source of infection
  • night sweats with no evidence of infection
  • progressive marrow failure (worsening anemia with hemoglobin <10 gm/dL and/or thrombocytopenia with platelet count <100,000/mm3)
  • massive or progressive splenomegaly (spleen >6 cm below left costal margin).

• Women must not be able to become pregnant (e.g. post menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. [Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.]

• Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.

• Accessibility to the site.

Exclusion Criteria:

• Chemotherapy, antibody therapy, surgery within 4 weeks of study enrollment.
• Exposure to any investigational agent within 30 days of the Screening Visit.
• Known CNS disease.
• Concurrent active malignancies except basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix.
• Laboratory values: Screening creatinine clearance (calculated by Cockcroft Gault formula) of less than 50 mL/minute, alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, total bilirubin greater than 3 times the upper limit of normal, white blood cell (WBC) count <3500/mm3, absolute neutrophil count <1000/mm3, hematocrit level <33% for females or <35% for males.
• Clinically evident congestive heart failure >class II of the New York Heart Association (NYHA) guidelines.
• Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
• History or signs of active coronary artery disease with or without angina pectoris.
• Serious myocardial dysfunction defined scintigraphically (MUGA, myocardial scintigram) or ultrasound determined absolute left ventricular ejection fraction (LVEF) <45% of predicted.
• Known HIV infection.
• Uncontrolled active, infection.
• Major surgery within 3 weeks prior to treatment.
• Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
• Any condition that in the opinion of the Investigator is unstable and could jeopardize the subject's participation in the study.