| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Previously Untreated Chronic Lymphocytic Leukemia (CLL) |
|
| 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 | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to evaluate the safety and tolerability of FCR+L compared with FCR alone in subjects with previously untreated CLL. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of this study is to evaluate the efficacy of FCR+L compared with FCR alone in subjects with previously untreated CLL. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Age ≥18 years at the time of informed consent.
3. Previously untreated CD23+ and CD20+ B-cell CLL as defined by NCI-WG Guidelines (1996).
4. Life expectancy >6 months in the opinion of the Investigator.
5. Subjects with Rai Stage III or IV (Binet Stage C), or Rai Stage I or II (Binet Stage A or B) if determined to have active disease as evidenced by massive or progressive
splenomegaly, massive or progressive lymphadenopathy, rapid doubling of peripheral
lymphocyte count, or B symptoms (see Appendix B, Staging Criteria – Modified Rai)
6. World Health Organization (WHO) Performance Status ≤2.
7. Normal ECG with QTc ≤450 msec for men and ≤460 msec for women. PR interval
(PRint) must be <240 msec and QRS complex <110 msec. T wave flattening and T wave inversion will be permitted.
8. All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 12 months after their last dose of study treatment. For further details of contraceptive requirements for this study.
9. Acceptable liver function at Screening:
• Bilirubin ≤2.0 mg/dL (34.2 μmol/L).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2 times the
upper limit of normal.
10. Acceptable hematologic status at Screening:
• Platelet count ≥50 × 109/L not supported by transfusion.
• Absolute neutrophil count (ANC) ≥1 × 109/L.
11. Acceptable renal function at Screening:
• Creatinine clearance calculated according to the formula of Cockroft and Gault
>50 mL/min.
• Serum creatinine ≤1.5 times the upper limit of normal.
12. Subjects receiving any medication known to affect the QTc interval must discontinue the use of the medication or be on a stable dose of the medication for at least 3 months or 5 half-lives (whichever is longer) prior to Study Day 1, and continue (whenever possible) at the same dose throughout the study. |
|
| E.4 | Principal exclusion criteria |
1. Any prior therapy for CLL, including radiotherapy, radioimmunotherapy, biological
therapy, chemotherapy, allogeneic/autologous bone marrow transplant, peripheral blood stem cell transplant, or other investigational therapy.
2. Known history of or positive test result for human immunodeficiency virus.
3. Known history of or positive test result for Hepatitis C virus (test for Hepatitis C virus antibody) or Heptatitis B virus (test for Hepatitis B Surface Antigen and Hepatitis B Core Antibody) at Screening.
4. Uncontrolled diabetes mellitus.
5. Uncontrolled hypertension.
6. Hypokalemia, as defined by potassium below the lower limit of normal in the central laboratory results at Screening.
7. Hypomagnesemia, as defined by magnesium below the lower limit of normal in the
central laboratory results at Screening.
8. New York Heart Association Class III or IV cardiac disease; myocardial infarction within the past 6 months prior to Study Day 1.
9. Arrhythmia (other than sinus arrhythmia) within 30 days prior to Study Day 1.
10. Evidence of active myocardial ischemia on ECG (new T wave changes with chest pain or presence of elevation of cardiac enzymes) within 30 days prior to Study Day 1.
11. Subjects with pacemakers.
12. Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter’s Syndrome, or prolymphocyte leukemia [PLL]).
13. Secondary malignancy requiring active treatment.
14. Any medical condition that would require long-term use (>1 month) of systemic
corticosteroids during study treatment, and use of systemic corticosteroids for treatment of CLL during the study for any time period.
15. Any serious nonmalignant disease or laboratory abnormality, which would confound the evaluation of AEs.
16. Active bacterial, viral, or fungal infections.
17. Any known family history of long QT syndrome.
18. Seizure disorders requiring anticonvulsant therapy.
19. Severe chronic obstructive pulmonary disease with hypoxemia.
20. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.
21. Clinically active autoimmune disease.
22. Presence or history of Coombs-positive hemolytic anemia.
23. Pregnant or currently breastfeeding at Screening.
24. Prior exposure to lumiliximab or any other anti-CD23 antibody.
25. Subjects with known hypersensitivity to Chinese hamster ovary cell proteins, murine proteins, or any component of fludarabine, cyclophosphamide, rituximab, or the lumiliximab investigational treatment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this study is to evaluate the safety and tolerability of FCR+L compared with FCR alone in subjects with previously untreated CLL. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| 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 | No |
| 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
|
| End of Study will be at the time the last subject on study has reached the Week 33 visit or when the last subject on study has withdrawn from the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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