B-Cell Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL, leukemia, chronic lymphocytic leukemia
Brief summary
A Study of Bafetinib as Treatment for Patients with Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Detailed description
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.
Interventions
DRUGbafetinib
250 mg orally twice daily. Treatment continues until clinically significant disease progression or unacceptable toxicity is documented.
Sponsors
CytRx
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the response rate (complete and partial), in subjects with relapsed or refractory B-Cell CLL | Upto 6 months or disease progression |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Events | 1 year |
Countries
United States
Outcome results
None listed