Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL)

NCT01510756 | Terminated Phase 2 Results DMC

• 1 other identifier: 110574
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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%.)

  3 months

Secondary Outcomes (2)

• 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.

  Two months following completion of treatment with sorafenib according to iwCLL guidelines.

• Safety and Tolerability

  3 months

Study Arms (1)

Sorafenib

EXPERIMENTAL

Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days).

Drug: Sorafenib

Interventions

Sorafenib DRUG

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.

Also known as: Nexavar

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thomas Kipps: lead
• Bayer: collaborator

Study Sites (1)

UCSD Medical Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Thomas Kipps, MD
• Organization: University of California, San Diego

tkipps@ucsd.edu

(858) 534-5400

Study Officials

• Thomas J. Kipps, M.D., Ph.D.

  UCSD Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 11, 2012
• First Posted: January 16, 2012
• Study Start: December 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 21, 2016
• Results First Posted: October 5, 2015

Record last verified: 2015-12

Locations

US (1)