E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
line or relapsed patients with Grade 1, 2 or 3a, CD20 , follicular non-Hodgkin s Lymphoma who respond to rituximab-containing induction therapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10016895 |
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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 evaluate the safety of rituximab maintenance therapy following a rituximab-containing induction regimen in first line or relapsed patients with follicular Non-Hodgkin s Lymphoma. |
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E.2.2 | Secondary objectives of the trial |
Further confirm the effectiveness of rituximab maintenance therapy with respect to Progression Free Survival PFS , Event Free Survival EFS , Time to Next Lymphoma Treatment TNLT , Overall survival OS and the partial response PR to complete response/complete response unconfirmed CR/Cru conversion rate while on rituximab maintenance therapy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed written informed consent form. 2. Histologically confirmed, CD20 , Grade 1, 2 or 3a follicular non-Hodgkin s lymphoma. 3. Patients must have received adequate induction therapy either as first line treatment or patients must have received adequate induction therapy as treatment for relapsed disease. Adequate induction therapy is defined as treatment with a minimum of 8 cycles of rituximab 375 mg/m2 body surface area BSA either as monotherapy, or combined with chemotherapy. The type of chemotherapy and the number of cycles added to 8 cycles of rituximab is according to the investigator s judgment e.g. 6 x CVP 8 x rituximab would be considered adequate for this study . 4. Patients must have a computerized tomography CT or Positron Emission Tomography PET or Magnetic Resonance Imaging MRI documented response to induction therapy PR, CR or CRu. Response assessment must be made within six weeks of study entry. 5. Induction therapy should have been completed to allow the first rituximab maintenance administration to occur eight to twelve weeks after day 1 of the last induction cycle. If patients are recovering from chemotherapy related toxicity from the most recent rituximab-containing induction therapy, they may receive their first rituximab maintenance therapy infusion up to six months after day 1 of the last cycle of induction therapy. 6. Patients must be 8805; 18 years old. 7. Patients must have a performance status 8804; 2 on the Eastern Cooperative Oncology Group ECOG scale. 8. Adequate haematological function within 28 days prior to their first rituximab maintenance infusion. This includes Haemoglobin 8805; 8.0g/dL 5.0 mmol/L Absolute neutrophil count ANC 8805; 1.5 x 109/L Platelet count 8805; 100 x 109/L. 9. Patients must have IgG levels 8805; 2g/L within 28 days prior to their first rituximab maintenance infusion. 10. Agree to use effective contraception, and agree not to become pregnant during participation in the study or within 12 months after the last rituximab maintenance infusion. Men agree not to father a child during participation in the study or within 12 months after the last rituximab maintenance infusion. |
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E.4 | Principal exclusion criteria |
1. Patients with poor compliance during induction therapy; judgment is up to investigators 2. Patients who had significant delays / interruptions in their induction therapy such that completion of the planned rituximab therapy was more than four months longer than the planned schedule. 3. Stable disease SD or progressive disease PD after most recent induction therapy. 4. Transformation to high-grade lymphoma secondary to low-grade follicular lymphoma . 5. Presence or history of central nervous system CNS lymphomatous disease e.g. CNS lymphoma or lymphomatous meningitis . 6. Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to 20 mg/day prednisone. 7. Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer. 8. Major surgery excluding lymph node biopsy within 28 days prior to inclusion. 9. Poor hepatic function total bilirubin 2.0 mg/dL 34 mol/L , alanine- and aspartate-amino-transferase ALT, AST 3 x the upper limit of normal ULN unless these abnormalities are related to lymphoma. 10. Patients who have known human immuno-deficiency virus HIV infection or active hepatitis B virus HBV or hepatitis C virus HCV infection. 11. Serious underlying medical conditions, which could impair the ability of the patient to participate in the study e.g. uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease, uncontrolled hypertension or pre-existing cardiac condition . Judgment is up to the investigator. 12. Pregnant patients cannot enter the study. A negative serum pregnancy test is required for women of childbearing potential within seven days prior to first rituximab maintenance therapy infusion. 13. Breast-feeding patients are not permitted to enter the study. 14. Life expectancy of less than 6 months. 15. Known sensitivity or allergy to murine products. 16. Treatment within a clinical study within 30 days prior to study entry. 17. Patient unable to provide informed consent or patients under protection from a guardian. 18. Active Infection requiring treatment, or chronic recurrent infection e.g. osteomyelitis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
safety of rituximab maintenance therapy |
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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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
studio in aperto, non comparativo |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |