Clinical trial NCT01144260: Study of Bafetinib as Treatment for Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)
Official title: A Pilot Phase II Study of Bafetinib (INNO-406) as Treatment for Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-Cell Chronic Lymphocytic Leukemia
Keywords: CLL
leukemia
chronic lymphocytic leukemia
Lead sponsor: CytRx
Sponsor class: INDUSTRY
First posted: 2010-06-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To evaluate the response rate (complete and partial), in subjects with relapsed or refractory B-Cell CLL
timeFrame: Upto 6 months or disease progression
Secondary outcomes:
measure: Adverse Events
timeFrame: 1 year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Houston
country: United States
facility: UT M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: CytRx
name: Daniel Levitt, M.D., Ph.D.
role: STUDY_DIRECTOR
References: