Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL)

• Status: Terminated
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2 trial to evaluate the activity of sorafenib in relapsed or refractory CLL patients with an iwCLL-WG indication to receive therapy.

Sorafenib is an orally active multikinase inhibitor, which targets the RAF/MEK/ERK signaling pathway as well as several receptor tyrosine kinases. It is FDA approved for the treatment of hepatocellular carcinoma and renal cell carcinoma. Preclinical studies in the investigators laboratory demonstrated that sorafenib is cytotoxic to CLL cells.

The primary objective of the study is to determine the overall response rate of Sorafenib in previously treated CLL patients. All patients will receive sorafenib at 400 mg twice daily continuously for three months and then assessed for response. Responding patients may elect to continue on treatment for an additional 9 months.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thomas Kipps
• Collaborator: Bayer
• Treatments: Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

• Diagnosis of relapsed or refractory CLL.

• Experiencing progressive disease with an iwCLL-WG indication to receive therapy.

• Age ≥ 18 years.

• ECOG performance status ≤ 2 at study entry.

• Adequate organ and marrow function as defined below:

• platelets ≥ 50 x 109/L

• serum creatinine ≤ 1.5 mg/dL

• total bilirubin ≤ 1.5 mg/dL

• AST(SGOT)/ALT(SPGT) ≤ 2 X institutional upper limit of normal or if known liver involvement <5X institutional upper limit of normal

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• No investigational agents within 28 days prior to entering the study.

• No concurrent use of other anti-cancer agents or treatments.

• No congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (beginning within the last 3 months) or myocardial infarction within the past 6 months.

• No known brain metastases (progressive neurologic dysfunction may confound the evaluation of neurologic and other adverse events).

• No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

• No uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.

• No known active Hepatitis or HIV.

• No history of allergic reactions attributed to compounds sorafenib or its excipients.

• No uncontrolled intercurrent illness such as ongoing or active infection (fungal, bacterial, and/or viral), CTCAE grade 2 or greater.

• No thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• No serious non-healing wound, ulcer, or bone fracture.

• No major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

• No condition that may impair the patient's ability to swallow whole pills.

• Patient must not have any malabsorption problem.

• Patients receiving St. John's Wort or rifampin (rifampicin) are ineligible.

• Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP) are ineligible.

• Patients must not be experiencing psychiatric illness/social situations that would limit compliance with study requirements.

• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from CLL except cervical cancer in-situ, treated basal cell carcinoma, squamous cell carcinoma of the skin, or superficial bladder tumor (Ta and Tis). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before study entry are allowed. All cancer treatments must be completed at least 3 years prior to study entry (ie, signature date of the informed consent form).