E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Follicular non Hodgkin's Lymphoma (NHL) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
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 |
to further confirm the effectiveness of rituximab maintenance therapy with respect to Progession 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) converstion rate while on rituximab maintenance therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed written informed consent form. (For Germany see also section 17.11.1) 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 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 (1 week before, or 2 weeks after, the period of eight to twelve weeks may be tolerated if these changes are due to documented administrative problems at the study site beyond the contol of the site staff). • 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 ≥ 18 years old. 7. Patients must have a performance status ≤ 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 ≥ 8.0g/dL (5.0 mmol/L) • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L • Platelet count ≥ 100 x 109/L. 9. Patients must have immunglobulin G (IgG) levels ≥ 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. (For Germany see also section 17.11.1) |
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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 their first rituximab maintenance infusion. 9. Poor hepatic function: total bilirubin > 2.0 mg/dL (34 µmol/L), alanine- amino-transferase (ALT) > 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. (For Germany see also section 17.11.1) 16. Treatment within a clinical study within 30 days prior to study entry. (For Germany see also section 17.11.1) 17. Patient unable to provide informed consent or patients under protection from a guardian. (For Germany see also section 17.11.1) 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) |
The primary endpoint of this study is safety. The following safety variables will be monitored during this study: AEs, laboratory tests and vital signs |
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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 | Information not present in EudraCT |
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) | 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 | 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 | 20 |
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 | 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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The end of study is defined as the date of the last 12 month follow up visit following rituximab maintenance therapy for the last patient included, or sooner if all patients have progressed, died, or withdrawn from the study. |
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 5 |