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

B-Cell Chronic Lymphocytic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144260
• Other study ID #: BAFETINIB-P2-CLL-01
• Status: Completed
• Phase: Phase 2
• First received: June 9, 2010
• Last updated: May 14, 2013
• Start date: June 2010
• Est. completion date: April 2013

Study information

• Verified date: May 2013
• Source: CytRx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2013
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-Cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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

Locations

Country	Name	City	State
United States	City of Hope National Medical Center	Duarte	California
United States	UT M.D. Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CytRx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the response rate (complete and partial), in subjects with relapsed or refractory B-Cell CLL		Upto 6 months or disease progression	No
Secondary	Adverse Events		1 year	Yes