E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle Cell Lymphoma |
Mantle Cell Lymphoma |
|
E.1.1.1 | Medical condition in easily understood language |
Mantle Cell Lymphoma |
Mantle Cell Lymphoma |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061275 |
E.1.2 | Term | Mantle cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 Overall Response Rate(ORR) (expressed as CR and PR) in MCL patients treated with MabThera plus chemotherapy |
|
E.2.2 | Secondary objectives of the trial |
To determine Overall Survival(OS), Progression Free Survival (PFS) and toxicity of the treatment and to identify predictive factors for a positive prognosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed mantle cell lymphoma (MCL) according to WHO classification prior to study inclusion. The diagnosis has to be confirmed by immunophenotyping CD 20+ (CD5+, CD23-, sIgM, cyclin D1, Ki 67 )
2. At least 1 measurable or assessable site of disease; in case of bone marrow infiltration only, bone marrow aspiration/ biospy is mandatory for all staging evaluations
3. Patients with untreated MCL (excepting radiotherapy used for palliative, not for curative purposes) at any stage requiring therapy in the opinion of the treating physician that are not eligible for Autologous Stem Cell Transplant.
4. Age >18 years old
5. ECOG PS 0-2
6. Life expectancy >6 months
7. Known MIPI at the time of diagnosis
8. Women of child bearing potential must have negative pregnancy test and agree to use effective contraception during entire study therapy and 12 months thereafter; men must agree not to father a child during entire study therapy and 12 months thereafter
9. Adequate hematological function within 28 days prior to the first rituximab infusion:
• Haemoglobin≥ 8 g/dL
• Absolute neutrophile count ≥1.5x109/L
• Platelet count≥100x109/L
10. Adequate hepatic and renal function:
• Transaminases (ASAT and ALAT) ≤3 x upper limit of normal (ULN)
• Total bilirubin ≤2 x ULN
• Alkaline phosphatase ≤2 x ULN
• Creatinine ≤2 mg/dL or calculated creatinine clearance ≥50 mL/min
11. LVEF≥50 %
12. Patients willing and able to comply to study protocol for the entire study duration
13. Patient’s written informed consent
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to murine proteins or chemotherapy regimen
2. Previous first line therapy
3. History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or in situ cervical carcinoma within the last 5 years
4. Active opportunistic infections requiring treatment
5. Active HIV infection, hepatitis B or C
6. Serious underlying conditions which could impair the patient ability to take part in the study (uncontrolled diabetes mellitus, severe cardiac dysfunction or angina, gastric ulcer, pulmonary, endocrinological or neurological disorder, psychiatric illness, active autoimmune disease)
7. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary disease or cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months
8. Pregnancy and lactation
9. Creatinine clearance ≤30 mL/min
10. Major surgery other than diagnostic surgery within 28 days prior to study entry
11. Patients regularly taking corticosteroids during the last 4 weeks
12. Treatment within a clinical trial within 30 days before study entry
13. Patients unable to comply to study protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine Overall Response Rate(ORR) (expressed as CR and PR) in MCL patients treated with MabThera
plus chemotherapy |
no |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To determine Overall Survival(OS), Progression Free Survival (PFS) and toxicity of the treatment and to identify
predictive factors for a positive prognosis. |
no |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
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 | 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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Last Visit of the Last Subject |
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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 | |
E.8.9.1 | In the Member State concerned days | |