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

Sponsor

CytRx (Industry)

Overall Status

Completed

CT.gov ID

NCT01144260

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
B-Cell Chronic Lymphocytic Leukemia	Drug: bafetinib	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bafetinib	Drug: bafetinib 250 mg orally twice daily. Treatment continues until clinically significant disease progression or unacceptable toxicity is documented. Other Names: INNO-406

Arm

Intervention/Treatment

Experimental: Bafetinib

Drug: bafetinib

250 mg orally twice daily. Treatment continues until clinically significant disease progression or unacceptable toxicity is documented.

Other Names:

INNO-406

Outcome Measures

Primary Outcome Measures

To evaluate the response rate (complete and partial), in subjects with relapsed or refractory B-Cell CLL [Upto 6 months or disease progression]

Secondary Outcome Measures

Adverse Events [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.