study of bafetinib as treatment for relapsed or refractory b-cell chronic lymphocytic leukemia (b-cll)

Conditions: B-Cell Chronic Lymphocytic Leukemia

Summary: 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.

Eligibility criteria:
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.

Keywords: cll leukemia chronic lymphocytic leukemia