Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01510756
Recruitment Status : Terminated (slow enrollment)
First Posted : January 16, 2012
Results First Posted : October 5, 2015
Last Update Posted : January 21, 2016
Information provided by (Responsible Party):
Thomas Kipps, University of California, San Diego

Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Sorafenib Phase 2

Detailed Description:

The UCSD Moores Cancer is conducting a Phase 2 clinical trial to evaluate the activity of sorafenib in relapsed or refractory CLL patients.

Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor with effects on tumor proliferation and tumor angiogenesis. It was initially selected based on inhibition of the serine/threonine kinases Raf-1 and wild-type B-Raf, which are pivotal components of the Ras/Raf/MEK/ERK signaling pathway. CLL cells derive survival support from their microenvironment, in part by activation of this pathway. Preclinical studies performed in our lab demonstrated that sorafenib was cytotoxic to CLL cells, including those from patients with more aggressive disease and from patients with chemotherapy (fludarabine) resistant disease.

The purpose of this study is to evaluate for evidence of anti-leukemic activity / clinical activity of sorafenib by assessing decrease in absolute lymphocyte count (ALC)/leukemia cell counts, lymphadenopathy, splenomegaly, and leukemia infiltration of bone marrow and to assess the impact of sorafenib on the CLL B cells through corollary studies. Patients will continue treatment for up to 3 monthly cycles unless toxicity or progressive disease. Patients with noted stable disease (or better) in the absence of significant toxicity will be allowed to receive another 1-9 cycles of single agent sorafenib. All patients will be assessed for response following 3 cycles of treatment and/or following all therapy per iwCLL-WG 2008 guidelines.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Translational Study of Sorafenib for the Treatment of Chronic Lymphocytic Leukemia Patients
Study Start Date : December 2011
Actual Primary Completion Date : May 2014
Actual Study Completion Date : December 2014

Arm Intervention/treatment
Experimental: Sorafenib
Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days).
Drug: Sorafenib
Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days). Subjects without significant toxicity or progressive disease may elect to continue treatment for a total of twelve cycles.
Other Name: Nexavar

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 3 months ]
    Determination of absolute lymphocyte count (ALC), lymphadenopathy, splenomegaly, and/or marrow leukemia as measured by 4-color flow minimal residual disease (MRD) panel after 3 cycles of study treatment. (Decrease in absolute lymphocyte count by 50%, decrease in lymphadenopathy (sum of lymph node product) by 50%, decrease in splenomegaly by 50%, or decrease in leukemia infiltration of the bone marrow by 50%.)

Secondary Outcome Measures :
  1. To Determine the iwCLL-WG Defined Overall Response Rate (ORR) - Complete Response (CR) and Partial Responses (PR) to 3 Cycles of Sorafenib Therapy and Following the Completion of All Therapy. [ Time Frame: Two months following completion of treatment with sorafenib according to iwCLL guidelines. ]
    A response assessment must be performed 2 months following completion of therapy to document responses, including a bone marrow if in clinical response (CR) and a computed tomography (or magnetic resonance imaging scan [MRI]) if initial imaging was abnormal or physical examination inconclusive.

  2. Safety and Tolerability [ Time Frame: 3 months ]
    Frequency, severity and relatedness of adverse events

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01510756

United States, California
UCSD Medical Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
Thomas Kipps
Principal Investigator: Thomas J. Kipps, M.D., Ph.D. UCSD Medical Center

Responsible Party: Thomas Kipps, Professor of Medicine, University of California, San Diego Identifier: NCT01510756     History of Changes
Other Study ID Numbers: 110574
First Posted: January 16, 2012    Key Record Dates
Results First Posted: October 5, 2015
Last Update Posted: January 21, 2016
Last Verified: December 2015

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs