A Phase I/II Study of Lumiliximab in Combination With Fludarabine, Cyclophosphamide, and Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia
Inclusion Criteria:
- Age: 18 years and older
- Diagnosis of B-cell CLL by International Workshop on CLL (IWCLL) response criteria
- Relapsed CD23+ B-cell CLL
- Rai Stage III or IV, or Rai Stage I or II if determined to have disease progression
as evidenced by rapid doubling or peripheral lymphocyte count, progressive
lymphadenopathy, progressive splenomegaly, or B symptoms
- Prestudy WHO Performance Status less than or equal to 2
- Signed, written Institutional Review Board (IRB)-approved informed consent
- Men & women of reproductive potential must agree to follow accepted birth control
methods during treatment for 3 months after completion of treatment
- Acceptable liver function: Bilirubin less than or equal to 2.0 mg/dL (26 µmol/L), AST
(SGOT) &/or ALT (SGPT) less than or equal to 2 times upper limit of normal
- Acceptable hematologic status: Platelet count less than or equal to 50 x 10^9/L, ANC
less than or equal to 1 x 109/L
- Acceptable renal function: Serum creatinine less than or equal to 1.5 times upper
limit of normal
Exclusion Criteria:
- Subjects who did not respond to prior FCR therapy (relapsed within 6 months of the
last dose).
- Cancer radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other
investigational therapy within 4 weeks prior to Study Day 1
- Previous exposure to lumiliximab or other anti-CD23 antibodies
- Subjects who have had a prior allogenic bone marrow transplant (BMT) or autologous
BMT or peripheral stem-cell transplant (PBSCT)
- Known infection with HIV, hepatitis B, or hepatitis C
- Uncontrolled diabetes mellitus
- Uncontrolled hypertension
- Transformation to aggressive B-cell malignancy (e.g., larger B-cell lymphoma,
Richter's Syndrome, or prolymphocyte leukemia (PLL)
- Subjects with secondary malignancy requiring active treatment (except hormonal
therapy)
- Subjects with medical conditions currently requiring long-term use (less than 1
month) of systemic corticosteroids
- Serious nonmalignant disease or laboratory abnormality, which, in the opinion of the
investigator &/or sponsor, would compromise protocol objectives
- Active uncontrolled bacteria, viral, or fungal infections
- New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months prior to Study Day 1, unstable arrhythmia, or evidence of
ischemia on ECG within 14 days prior to Study Day 1
- Seizure disorders requiring anticonvulsant therapy
- Severe chronic obstructive pulmonary disease with hypoxemia
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1
- Clinically active autoimmune disease
- Subjects with a history of fludarabine-induced autoimmune cytopenia
- Pregnant or currently breast-feeding