A Pilot Phase II Study of Bafetinib (INNO-406) as Treatment for Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)
- 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
- 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
- either weight loss ≥10% within the past 6 months or extreme fatigue due to
- 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.
- 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.