Lumiliximab in Combination With FCR in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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This is an open label, Phase I/II, dose escalation research study of an investigational product called lumiliximab, given with FDA (Food and Drug Administration) approved products fludarabine, cyclophosphamide, and rituximab (FCR). The study duration is 17 visits over 42 months or until your disease progresses and you require additional CLL therapy. The total duration of participation in the study will be approximately 4 years, however your disease status will be followed indefinitely (forever).

Official Title
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A Phase I/II Study of Lumiliximab in Combination With Fludarabine, Cyclophosphamide, and Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Lumiliximab with FCR


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lumiliximab with FCR|Dose, schedule, and duration specified in protocol|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the safety profile |  | monthly until month 12, then every 3 months for 24 months, then every 6 months until month 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetics of lumiliximab and rituximab |  | 6 months |