E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effectiveness of lumiliximab when used in combination with FCR compared with FCR alone for the treatment of subjects with relapsed CLL. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate and compare the safety profile of subjects treated with lumiliximab in combination with FCR versus FCR alone in subjects with relapsed CLL. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
 Signed, written Ethics Committee (EC)-approved informed consent form.  Relapsed CD23+ and CD20+ B-cell CLL as defined by National Cancer Institute-Working Group (NCI-WG) Guidelines.  Subjects who have received no more than 2 prior single agent or combination treatments for progressive disease.  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 ヨ Modified Rai).  World Health Organization (WHO) Performance Status 2.  Age 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 2.0 mg/dL (26 ᄉmol/L).  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2 times upper limit of normal.  Acceptable hematologic status:  Platelet count 50  109/L should be unsupported by transfusion.  Absolute neutrophil count (ANC) 1  109/L.  Acceptable renal function:  Creatinine clearance calculated according to the formula of Cockroft and Gault >50 mL/min.  Serum creatinine 1.5 times upper limit of normal. |
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E.4 | Principal exclusion criteria |
 Subjects who are refractory to fludarabine and rituximab (FR), fludarabine and cyclophosphamide (FC), or FCR. Refractory is defined as not achieving at least a partial response for a minimum duration of 6 months as determined by treating physician.  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メ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 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 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
complete response (CR) rate |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |