E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
With an annual incidence of 3/100,000 chronic lymphocytic leukaemia is the most common leukaemia in western countries. Pathogenetically and cytomorphologically CLL belongs to the group of low-grade non-Hodgkin's lymphomas. More than 90 % of the cases are derived from B-lymphocytes. |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
The objective of this study is to determine the value of immunochemotherapy with FCR in comparison with chemotherapy with FC alone in the first-line therapy of B-CLL. The study is to answer the following questions:
• Is combined immunochemotherapy with FCR superior in terms of progression free survival to chemotherapy with FC alone in the first-line therapy of B-CLL?
• Is combined immunochemotherapy with FCR a safe alternative to FC chemotherapy alone with regards to the adverse effects?
|
|
E.2.2 | Secondary objectives of the trial |
- Event-free survival
- Overall survival
- Disease-free survival
- Duration of remission
- Time to new CLL treatment or death
- Rates of molecular, complete and partial remission
- Response rates and survival times in biological subgroups
- Rates of treatment-related adverse effects
- Pharmacoeconomic impact
- Quality of life
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•B-CLL confirmed according to NCI Working Group criteria [1]
•Binet stage C as well as Binet stage B requiring treatment
All patients must fulfill the criteria of disease requiring treatment. Disease requiring treatment is defined as:
•Binet stage C
•Binet stage B plus at least one of the following signs or symptoms:
- B symptoms (night sweats, weight loss > or = 10% within the previous 6 months, fevers > 38°C or 100.4°F for > or = 2 weeks without evidence of infection) or constitutional symptoms (fatigue)
- Continuous progression (doubling of peripheral lymphocyte count < 6 months AND absolute lymphocyte count > 50 G/l)
- evidence of progressive marrow failure as manifested by the development / worsening of anemia and/or thrombocytopenia
- massive, progressive or painful splenomegaly or hypersplenism
- massive lymph nodes or lymph node clusters (> 10 cm in longest diameter), danger of organ complications through large lymphomas (e.g. vascular compression, e.g. tracheal narrowing) or progressive lymphadenopathy
- Occurrence of symptomatic hyperviscosity problems at leucocyte counts > 200 G/l (symptomatic leucostasis)
• No previous treatment of the CLL by chemotherapy, radiotherapy or immunotherapy.
• Alkaline phosphatase and transaminases ≤ 2 x ULN
• A negative serum pregnancy test one week prior to treatment must be available both for pre-menopausal women and for women who are < 2 years after the onset of menopause.
• Willingness to use contraception for the entire duration of the treatment and 2 months thereafter
• Patient's written informed consent
• Age > or = 18 years
• Life expectancy > 6 months
• ECOG performance status 0-1
• Patient's written informed consent |
|
E.4 | Principal exclusion criteria |
• Stage Binet A
• Clinically significant auto-immune cytopenia, Coombs-positive haemolytic anaemia as judged by the treating physician.
• Active second malignancy currently requiring treatment (except basal cell carcinoma or tumour treated curatively by surgery)
• Pregnancy,and/or nursing
• Concomitant disease requiring prolonged use of glucocorticoids (> 1 month)
• Known hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or any of the study drugs
• CIRS score > 6
• Cerebral dysfunction which makes it impossible to perform chemotherapy
• Transformation to aggressive B-cell malignancy (eg diffuse large cell lymphoma, Richter's syndrome, or prolymphocytic leukaemia) .
• Active bacterial, viral or fungal infection. Although testing for hepatitis B is not mandatory, this should be considered for all patients considered at high risk of hepatitis B infection and in endemic areas. Patients with any serological evidence of current or past hepatitis B infection are excluded unless the serological findings are clearly due to vaccination.
• Total bilirubin > 2 x ULN
• Creatinine clearance < 70 ml/min calculated according to the formula of Cockcroft and Gault
• Any coexisting medical or psychological condition that would preclude participation in the required study procedures.
• Treatment with any other investigational agent, or participating in another clinical trial within 30 days prior to entering this study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Median observation time at time of analysis was approximately 21 months. |
|
E.5.2 | Secondary end point(s) |
1. Event-free Survival (EFS)
2. Overall Survival (OS)
3. Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Median observation time at time of analysis was approximately 21 months. |
|
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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5.1 | Number of sites anticipated in the EEA | 167 |
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 | No |
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 |
Australia |
Austria |
Belgium |
Czech Republic |
Denmark |
France |
Germany |
Israel |
Italy |
New Zealand |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the trial is 31st October 2011 or your country approval date for this amendment after the last patient entered (unless all patients have died or withdrawn from the study before then). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |