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A Phase II Study of BAY 43-9006 in Relapsed Chronic Lymphocytic Leukemia

Phase 2
18 Years
Not Enrolling
Refractory Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia

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Trial Information

A Phase II Study of BAY 43-9006 in Relapsed Chronic Lymphocytic Leukemia


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.


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.

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

- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Objective overall response rate

Outcome Description:

The 95% confidence intervals should be provided.

Outcome Time Frame:

Up to week 25

Safety Issue:


Principal Investigator

John Godwin

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Refractory Chronic Lymphocytic Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Chronic Lymphocytic Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470