E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CD20-positive B-cell chronic lymphocytic leukemia |
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MedDRA Classification |
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 primary objective of this study is to demonstrate that the combination of rituximab and chlorambucil is safe by examining the adverse event profile. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine the following outcome measures:
•Overall response rate (ORR), complete response rate (CR), partial response rate (PR) and nodular partial response (nPR) •Progression-free survival •Disease-free survival •Duration of response •Overall survival •Proportion of patients who achieved eradication of detectable minimal residual disease
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with CD20-positive B-cell CLL (NCI criteria) who are previously untreated 2. Patients with progressive Binet stage B, or C requiring therapy according to NCI criteria 3. Age ≥ 18 years 4. Signed written informed consent 5. Life expectancy > 6 months 6. Eastern Co-operative Oncology Group (ECOG) performance status </= 2 7. Absolute Neutrophil Count (ANC) ≥ 1x109/L 8. Platelet count >/= 50x109/L, unless due to involvement of bone marrow by CLL 9. Total bilirubin </= 2xULN 10. Alkaline phosphatase and transaminases </= 2xULN 11. A negative serum pregnancy test up to one week prior to the first cycle of treatment must be available both for pre-menopausal women and for women who are </= 2 years after the onset of menopause
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E.4 | Principal exclusion criteria |
1. Patients with other malignancy within the last 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ of the breast treated with lumpectomy alone with curative intent. 2. Patients with known concomitant haematological malignancy; e.g. myelodysplastic syndromes. 3. Patients with reproductive potential not willing to use effective method of contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) 4. Patients who have received previous treatment for CLL 5. Patients with active bacterial, viral, or fungal infection requiring systemic therapy 6. Patients with a history of severe cardiac disease; e.g. New York Heart Association (NYHA) Functional Class III or IV heart failure [Appendix 3], myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina 7. Patients with significant autoimmune cytopenia as assessed by the physician (Coombs positive patients without clinical signs of autoimmune haemolytic anaemia are eligible for study entry) 8. Patients with severe chronic obstructive pulmonary disease (COPD) with hypoxemia 9. Patients with uncontrolled diabetes mellitus (defined as HbA1c >/= 10%) 10. Patients with uncontrolled hypertension (normally defined as blood pressure repeatedly >/= 140/90mmHg, but investigator discretion to be used) 11. Patients with transformation to aggressive B-cell malignancy (e.g. large B-cell lymphoma, Richter’s syndrome or polymorphocytic leukaemia (PLL)) 12. Patients who have received any investigational treatment, or participating in another clinical trial, within 30 days of study start 13. Patients with known Human Immunodeficiency Virus (HIV) infection, or active Hepatitis B (HBV) or Hepatitis C (HCV) infection. 14. Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins 15. Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent. 16. Hypersensitivity to chlorambucil or to any of the excipients
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to demonstrate that the combination of rituximab and chlorambucil is safe.
The following safety parameters will be monitored during the study: AEs, SAEs, laboratory tests and physical examination (weight, vital signs and cardiopulmonary examination)
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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Last Patient Last Visit, i.e. 24 months after the last patient received the last MabThera treatment (see protocol section 3.1.3.) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |