Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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This is a randomized (1:1), open-label, multicenter, active-controlled study in patients with previously treated CD23+ and CD20+ relapsed CLL. Patients will receive treatment with either lumiliximab in combination with FCR or FCR alone.

Official Title
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A Randomized, Open Label, Multicenter, Phase 2 Study to Evaluate the Safety and Efficacy of Lumiliximab in Combination With Fludarabine, Cyclophosphamide, and Rituximab Versus Fludarabine, Cyclophosphamide, and Rituximab Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: FCR + Lumiliximab
* Drug: FCR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed, written EC-approved informed consent form. Diagnosis of relapsed CD23+ and CD20+ B cell CLL as defined by NCI WG guidelines. Subjects who have received at least 1 but no more than 2 prior single agent or combination treatments for CLL. Rai Stage III or IV (Binet Stage C), or Rai Stage I or II (Binet Stage A or B) if determined to have disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms (Staging Criteria - Modified Rai). WHO Performance Status less than or equal to 2. Age greater than or equal to 18 years. Male and female subjects of reproductive potential must agree to follow accepted birth control methods during treatment and for 12 months after completion of treatment. Acceptable liver function: bilirubin less than or equal to 2.0 mg/dL (26 µmol/L); AST and ALT less than or equal to 2 times upper limit of normal. Acceptable hematologic status: platelet count greater than or equal to 50 x 10^9/L should be unsupported by transfusion; ANC greater than or equal to 1 x 10^9/L. Acceptable renal function: creatinine clearance calculated according to the formula of Cockcroft and Gault >50 mL/min; serum creatinine less than or equal to 1.5 times upper limit of normal. Exclusion Criteria: Subjects who are refractory to the following combination therapies: purine analogue + R, purine analogue + C, or purine analogue + CR. Refractory is defined as not achieving at least a PR for a minimum duration of 6 months as determined by treating physician. Purine analogues include fludarabine, pentostatin and cladribine. 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. Prior autologous or allogeneic BMT or hematopoetic stem cell transplant. Known infection with HIV, hepatitis B, or hepatitis C. Although testing for hepatitis B or hepatitis C is not mandatory, this should be considered for all subjects considered at high risk of hepatitis B or hepatitis C infection and in endemic areas. Subjects with any serological evidence of current or past hepatitis B or hepatitis C exposure are excluded unless the serological findings are clearly due to vaccination. Uncontrolled diabetes mellitus. Uncontrolled hypertension. Transformation to aggressive B-cell malignancy (e.g., large B cell lymphoma, Richter's Syndrome, or PLL). Secondary malignancy requiring active treatment (except hormonal therapy). Any medical condition that would require long-term use (>1 month) of systemic corticosteroids during study treatment. However, steroid use less than or equal to 1 month is permissible during the study. Any serious nonmalignant disease or laboratory abnormality, which in the opinion of the Investigator and/or Sponsor would compromise protocol objectives. Active uncontrolled bacterial, 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 30 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. History of fludarabine-induced autoimmune cytopenia (as judged by the Investigator) or Coombs-positive haemolytic anemia. Pregnant or currently breastfeeding.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>FCR F (Fludarabine): 25 mg/m2 daily, every four weeks for 21 weeks C (Cyclophosphamide): 250 mg/m2 daily, every four weeks for 21 weeks R: (Rituximab): Day 1 50 mg/m2, Day 3 325 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks | Drug: FCR<br>* Dose, schedule, and duration specified in protocol<br>|
| Experimental: 2<br>FCR + Lumiliximab (L) L (Lumiliximab): Day 2 50 mg/m2, Day 4 450 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks. F (Fludarabine): 25 mg/m2 daily, every four weeks for 21 weeks C (Cyclophosphamide): 250 mg/m2 daily, every four weeks for 21 weeks R: (Rituximab): Day 1 50 mg/m2, Day 3 325 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks | Drug: FCR + Lumiliximab<br>* Dose, schedule, and duration specified in the protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) rate |  | Every 3 months until all patients have reached at least week 33 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to event variables (progression free survival, duration of response, time to next therapy, time to progression and overall survival) |  | Every 3 months until all patients have reached at least week 33 | 
| Response variables |  | Every 3 months until all patients have reached at least week 33 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD23+/CD20+ B-cell CLL, CLL