- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00303966
Sorafenib in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
A Phase II Study of BAY 43-9006 in Relapsed Chronic Lymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the objective response rate in patients with recurrent chronic lymphocytic leukemia (CLL) treated with sorafenib.
II. Determine the toxicity in patients treated with sorafenib.
SECONDARY OBJECTIVES:
I. Correlate bone marrow angiogenesis, CLL tumor cell expression of vascular endothelial growth factor (VEGF), VEGF receptors (flt-1, KDR, flt-4 and neuropilin-1), basic fibroblast growth factor, and plasma interleukin-8 levels with response.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Illinois
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Chicago, Illinois, United States, 60637-1470
- University of Chicago Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) by NCI-WG immunophenotype and blood criteria
Documentation of current or prior peripheral blood (PB) or bone marrow (BM) immunophenotype compatible with CLL
- Patients who currently do not have > 5,000/mm³ absolute lymphocytosis are eligible if they have previously met PB lymphocytosis criteria and have a current immunophenotype documenting monoclonal B lymphocytosis morphologically and immunophenotypically compatible with CLL
Intermediate-risk (Rai stage I or II) or high-risk (Rai stage III or IV) disease, including any of the following:
- Rai stage I disease with lymphocytosis and enlarged nodes
- Rai stage II disease with lymphocytosis plus splenomegaly and/or hepatomegaly (nodes positive or negative)
- Rai stage III disease with lymphocytosis plus anemia
- Rai stage IV disease with lymphocytosis and thrombocytopenia
Must require treatment with active disease, experiencing disease related symptoms, or having deterioration of blood counts, meeting ≥ 1 of the following criteria:
Presence of ≥ 1 of the following disease-related symptoms:
- Weight loss > 10% within the past 6 months
- Extreme fatigue (i.e., ECOG performance status 2: cannot work or unable to perform usual activities)
- Fever > 100.5°F for 2 weeks without evidence of infection
- Night sweats without evidence of infection
- Evidence of progressive marrow failure, as manifested by worsening of anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelet count < 100,000/mm³), and/or neutropenia (neutrophil count < 2,000/mm³)
- Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly or discomfort from splenomegaly
- Massive nodes or clusters (i.e., > 10 cm in longest diameter), progressive adenopathy, or discomfort from lymphadenopathy
- Deterioration of blood counts and/or progressive lymphocytosis, with an increase of ≥ 10% documented over a 2-month period OR an anticipated doubling time < 6 months
Relapsed disease
Must receive at least 1, but no more than 3, prior chemotherapy regimens with any cytotoxic agent or antibody therapy
No fludarabine refractory disease
- Responded to prior fludarabine without relapse or disease progression for at least 6 months
- Patients with a history of Coombs-positive hemolytic anemia are eligible provided recovery from treatment of hemolysis and off steroids
- No stage 0 CLL
- No known CNS involvement
- Life expectancy > 6 months
- ECOG performance status 0-2 OR Karnofsky performance status 70-100%
- Absolute neutrophil count ≥ 1,000/mm³
- Platelets ≥ 30,000/mm³
- Bilirubin ≤ 2 mg/dL
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min (for patients with creatinine levels above normal)
- No currently active second malignancy
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception prior to and during study participation
No uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg on 2 different measurements at least 1 day apart with either systolic or diastolic number meeting this definition
- Patients may later enter the study, if they have achieved stable BP (i.e., < 140/90 mm Hg) on a regimen of ≤ 2 drugs after 6-8 weeks of therapy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with the study requirements
- No active infection requiring systemic antibiotics
- No evidence of bleeding diathesis
- No evidence of bowel perforation or obstruction risk
- No swallowing dysfunction leading to difficulty taking the study drug
- See Disease Characteristics
- Recovered from prior therapy
- At least 2 weeks since prior antibiotic therapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- At least 12 weeks since prior monoclonal antibody
Concurrent warfarin for anticoagulation allowed provided all of the following are met:
- On a stable therapeutic dose
- INR ≤ 3
- No active bleeding or pathological condition that carries high-risk of bleeding
- No prior MAPK signaling inhibitor agents or anti-angiogenesis agents
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
- No other concurrent investigational agents
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (sorafenib tosylate)
Patients receive oral sorafenib twice daily on days 1-28.
Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
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Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: Up to week 25
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Objective response is defined as a complete (CR) or partial (PR) remission.
Complete remission is defined as no evidence of chronic lymphocytic leukemia (CLL) in marrow with normal hematopoiesis and no palpable lymphadenopathy.
Partial remission is defined as improvement in blood counts from baseline with >50% reduction in lymph nodes on examination.
These are definitions from the CLL International Working Group (IWG).
|
Up to week 25
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Time to Disease Progression
Time Frame: Up to 5.5 years
|
Time to disease progression will be defined as the time from treatment start until disease progression and will be evaluated using the Kaplan-Meier estimator.
Those who do not progress will be censored at the time that they were last known to be progression free.
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Up to 5.5 years
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Overall Survival
Time Frame: Up to 5.5 years
|
Overall survival will be defined as time from the start of treatment until death from any cause and will be evaluated using the Kaplan-Meier estimator.
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Up to 5.5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Mean Microvessel Density From Baseline to Week 25
Time Frame: Baseline and week 25
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Mean microvessel density will serve as a marker of angiogenesis (other markers includes hot spot density).
Will be examined using random-effects linear models.
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Baseline and week 25
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Changes in Vascular Endothelial Growth Factor (VEGF) From Baseline to Week 25
Time Frame: Baseline and week 25
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Changes in VEGF levels (post-pretreatment) will be assessed.
A negative value indicates a decrease with treatment.
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Baseline and week 25
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Changes in Plasma Level of Interleukin-8 (IL-8) From Baseline to Week 25
Time Frame: Baseline and week 25
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The change (post-pretreatment) will be calculated and tested using a paired t test.
A negative value indicates a decrease with treatment.
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Baseline and week 25
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wendy Stock, University of Chicago Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Sorafenib
Other Study ID Numbers
- NCI-2012-02688
- N01CM62201 (U.S. NIH Grant/Contract)
- 14194B
- UCCRC-14194B
- NCI-7071
- CDR0000462339
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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