E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treated Elderly Patients with Chronic B Lymphocytic Leukemia or patients with underlying pathology |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003948 |
E.1.2 | Term | B-Lymphocytic, CLL (Kiel Classification) refractory |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003947 |
E.1.2 | Term | B-Lymphocytic, CLL (Kiel Classification) recurrent |
E.1.2 | System Organ Class | 100000004864 |
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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 clinical benefit of dose intensive Rituximab in addition to Glucocorticoid in terms of response rate. |
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E.2.2 | Secondary objectives of the trial |
To determine progresion free and overall survival. To characterize the safety profile. To assess health related quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The diagnosis of CD20 positive chronic B lymphocytic leukemia (B-CLL) confirmed by biopsy or flow-cytometry.
2. Previously treated patients with stage Rai I-IV and progressive disease (according to IWCLL 2008 guidelines).
Active B-CLL is defined by at least one of the following:
At least one of the disease related symptoms:
1. Constitutional symptoms:
1.1. Weight loss > 10% within the previous 6 months;
1.2. Fatigue (e. g. WHO performance status ≥ 2);
1.3. Fever ≥38C ≥ 2 weeks without evidence of infection;
1.4. Night sweats for more than 1 month without evidence of infection.
2. Evidence of progressive marrow failure as manifested by development of, or worsening of, anemia and/or thrombocytopenia
3. Autoimmune hemolysis and / or thrombocytopenia poorly responsive to corticosteroid therapy.
4. Massive (i. e. ≥ 6 cm bellow left costal margin) or progressive or symptomatic splenomegaly.
5. Massive lymphadenopathy or conglomerates (i. e., ≥ 10 cm in largest diameter) or progressive or symptomatic lymphadenopathy.
6. Progressive lymphocytosis with an increase > 50% over a 2-month period or an anticipated doubling time of less than 6 months. In patients with initial blood lymphocyte counts of less than 30x109/L LDT should not be used as a single parameter to define atreatment indication.
Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for protocol therapy.
3. Either of the following:
3.1. 18 years of age or older with impaired performance status (CIRS>6) and /or
3.2. 65 years of age or older with any performance status.
4. Signed informed consent form. |
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E.4 | Principal exclusion criteria |
1. Intolerance to exogenous protein or known severe reaction to the administration of Rituximab.
2. Active infection.
3. Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study Day 1.
4. TBC or fungal infection within the past 6 months even if adequately controlled by treatment.
5. Severe organ deficiency preventing the participation in the study.
6. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.
7. Active peptic ulcer.
8. Inadequately controlled diabetes mellitus.
9. Suspected or confirmed B-CLL CNS disease.
10. Known to be HIV positive.
11. Difficult to control, uncooperative patients.
12. Allergic disorders in need of chronic glucocorticoid therapy.
13. Other oncological diseases requiring active treatment (except hormonal therapy).
14. Pregnancy and breastfeeding.
15. Patients of reproductive potential who are not using effective methods of contraception. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2-3 months after the end of treatment. |
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E.5.2 | Secondary end point(s) |
Progression free survival (PFS), Overall survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months after the end of treatment |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |