E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed (maximum of 5 relapses) or refractory, low-grade or follicular, CD20+, B-cell Non-Hodgkin’s Lymphoma (NHL) |
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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 objective of this study is to determine whether therapy with rituximab alters the immune response in relapsed or refractory, low-grade or follicular, CD20+, B-cell NHL subjects in comparison to untreated, age-matched control subjects.
The primary endpoint of the study is to determine whether treatment with rituximab causes a clinically significant effect on immunological recall response to tetanus vaccine in NHL subjects.
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E.2.2 | Secondary objectives of the trial |
The secondary endpoints of the study are: - To determine whether NHL subjects can mount a primary immune response to KLH after treatment with rituximab. - To determine whether NHL subjects treated with rituximab experience clinically significant changes in antibody titers to a panel of specific antigens: S. pneumoniae, influenza A, mumps, rubella, and varicella.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A signed, written informed consent form that has been approved by an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 2. Age equal to or greater than 40 years. 3. Subjects of reproductive potential must agree to follow accepted birth control methods for the duration of the study. 4. Relapsed (maximum of 5 relapses) or refractory, low-grade or follicular, CD20+, B-cell NHL. 5. Histological confirmation of low-grade or follicular, B-cell NHL prior to study entry. 6. Prestudy WHO performance status of 0, 1, or 2. 7. Expected survival equal to or greater than 1 year. 8. Acceptable hematologic status: - Platelet count equal to or greater than 75,000 plts/mm3. - Total White Blood Cell (WBC) count equal to or greater than 3000 cells/mm3. - Hemoglobin equal to or greater than 8.0 g/dL. 9. Acceptable liver function: - Bilirubin equal to or less than 2.0 mg/dL (26 micromol/L). - Alkaline phosphatase, ALT (SGPT) and AST (SGOT) equal to or less than 2 times upper limit of normal (ULN). 10. Acceptable renal function: Serum creatinine equal to or less than 2.0 mg/dL (177 micromol/L). 11. Fully recovered from all nonhematological toxicities associated with prior surgery, radiation treatments, chemotherapy, biological therapy, bone marrow transplant, investigational drugs, or immunotherapy. 12. Known history of tetanus toxoid immunization or positive tetanus titer at the screening visit. |
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E.4 | Principal exclusion criteria |
1. Active autoimmune disease. 2. Exposure to rituximab within 12 months prior to Day 1. 3. Chemotherapy within 3 months prior to Day 1. 4. Previous immunization with tetanus toxoid within 2 years prior to Day 1. 5. Previous exposure to Keyhole Limpet Hemocyanin (KLH). 6. Receipt of intravenous or intramuscular immunoglobulin (IVIG or IMIG) within 30 days of Day 1. 7. Known history of hepatitis or other hepatic disease HIV infection or AIDS. 8. Current use (including "recreational use") of any illicit drugs or history of drug or alcohol abuse within the 5 years prior to Day 1. 9. Prior diagnosis of aggresive NHL or mantle-cell lymphoma. 10. Chronic lymphocytic leukemia (CLL). 11. Small lymphocytic lymphoma (IWF A) with peripheral blood lymphocyte count greater than 5,000 cells/mm3. 12. History of other primary malignancy, with the exception of squamous cell carcinoma or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer for which the subject has not been disease-free for at least 3 years. 13. Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active, uncontrolled bacterial, viral or fungal infection or any other condition that would compromise protocol objectives in the opinion of the investigator and/or sponsor. 14. Known allergies or contraindications to tetanus toxoid or KLH. 15. Known allergy to shellfish. 16. Presence of protein-losing enteropathy. 17. Major surgery other that diagnostic surgery, within 4 weeks prior to Day1. 18. Participation in another clinical trial with an investigational agent or device within the last year. The subject cannot participate in any other clinical study with an investigational agent or device during the course of this study. 19. Pregnant or lactating female subjects.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is to determine whether treatment with rituximab causes a clinically significant effect on immunological recall response to tetanus vaccine in NHL subjects. |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Untreated, age-matched subjects |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
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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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Follow-up 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 | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |