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 - Lumiliximab in combination with FCR in the treatment of relapsed C

Conditions: Relapsed Chronic Lymphocytic Leukemia (CLL)
MedDRA version: 8.1Level: LLTClassification code 10008956Term: Chronic lymphatic leukaemia

Registration Number: EUCTR2006-002987-24-AT

Lead Sponsor: Biogen Idec Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 627

Inclusion Criteria

? Signed, written Ethics Committee (EC)-approved informed consent form.
? Diagnosed relapsed CD23+ and CD20+ B-cell CLL as defined by National Cancer Institute-Working Group (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).
? World Health Organization (WHO) Performance Status < or = 2.
? Age > or = 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 < or = 2.0 mg/dL (34.2 µmol/L).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? Acceptable hematologic status:
- Platelet count >or = 50 x 10exp9/L should be unsupported by transfusion.
- Absolute neutrophil count (ANC) > or = 1 x 109/L.
? Acceptable renal function:
- Creatinine clearance calculated according to the formula of Cockroft and Gault >50 mL/min.
- Serum creatinine < or =1.5 times upper limit of normal.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

? Subjects who are refractory to the following combination therapies: purine analogue+rituximab, purine analogue+cyclophosphamide, or purine analogue+cyclophosphamide and rituximab. 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, pentastatin, and cladribine.
? Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other investigational therapy within 4 weeks prior to Study Day.
? Previous exposure to lumiliximab or other anti-CD23 antibodies.
? Prior autologous or allogeneic bone marrow transplant (BMT) or hematopoetic stem cell transplant.
? Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Although testing for hepatitis B or hepatitis C is not mandatory, this should be considered for all subjects 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 prolymphocyte leukemia [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 ? 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 electrocardiogram (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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effectiveness of lumiliximab when used in combination with Fludarabine, Cyclophosfamide and Rituximab (FCR) compared with Fludarabine, Cyclophosphamide and Rituximab (FCR) alone for the treatment of subjects with relapsed CLL.;Secondary Objective: To evaluate and compare the safety profile of subjects treated with lumiliximab in combination with FCR versus FCR alone in subjects with relapsed CLL.;Primary end point(s): Investigator-determined CR rate without the use of CT scans.

Secondary Outcome Measures