E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Hodgkin Follicular Lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10003899 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of HuMax-CD20 in patients with Follicular Lymphoma who are refractory to rituximab as monotherapy or in combination with chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To determine the long-term efficacy, the safety and the pharmacokinetic profile of HuMax-CD20. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patient with follicular lymphoma grade 1 – 2 (defined according to WHO guidelines (World Helath Organization classification of tumours: patholgy and genetics of tumours of haematopietic and lymphoid tissues) 2) Refractory to rituximab given as monotherapy or in combination with any chemotherapy or to rituximab given as maintenance treatment following R-chemo defined as:
a. failure to achieve at least PR to rituximab given as monotherapy or in combination with any chemotherapy; or, b. disease progression while on rituximab (either given as monotherapy or in combination with any chemotherapy or during rituximab maintenance treatment following R-chemo); or, c. disease progression in responders within 6 months of the last dose of rituximab (either given as monotherapy or in combination with any chemotherapy or after rituximab maintenance treatment schedule following R-chemo)
Please note that patients should have received at least 4 infusions of rituximab (either given as monotherapy or in combination with any chemotherapy)
3) Tumor verified to be CD20+ positive from excisional lymph node biopsy . The excisional lymph node biopsy has to be redone if: no tissue is available for central review or if there is clinical suspicion that the follicular lymphoma has transformed to aggressive lymphoma/higher malignancy grade 4) CT scan in screening phase (based on local evaluation) showing: a. 2 or more clearly demarcated lesions with a largest diameter ≥ 1.5 cm, or b. 1 clearly demarcated lesion with a largest diameter ≥ 2,0 cm 5) ECOG Performance Status of 0, 1, or 2 6) Age ≥ 18 years 7) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out |
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E.4 | Principal exclusion criteria |
1) Previous autologous stem cell transplantation, within 6 months prior to Visit 2 2) Previous allogeneic stem cell transplantation 3) More than 1 previous radio immunotherapy regimen 4) Received radio immunotherapy within 3 months prior to Visit 2 5) Received any of the following treatments within 4 weeks prior to Visit 2: • Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues) • Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day 6) Received monoclonal antibodies, other than rituximab, within 3 months prior to Visit 2 7) Patients previously treated with anti-CD20 monoclonal antibodies, other than rituximab 8) Clinical suspicion that the follicular lymphoma transformed to aggressive lymphoma (e.g. B-symptoms, fast growing tumor or increasing LDH level) unless a new biopsy, just before study entry, confirms follicular lymphoma 9) Known CNS involvement of FL 10) Past or current malignancy, except for: • Follicular Lymphoma • Cervical carcinoma Stage 1B or less • Non-invasive basal cell and squamous cell skin carcinoma • Malignant melanoma with a complete response of a duration of > 10 years • Other cancer diagnoses with a complete response of a duration of > 5 years 11) Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C 12) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities 13) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 14) History of significant cerebrovascular disease 15) Known HIV positive 16) Positive serology for hepatitis B defined as a positive test for HBsAg and/or a combination of a positive test for anti-HBs and anti-HBc 17) Screening laboratory values: • platelets < 50 x 10^9/L (unless due to FL involvement of the bone marrow) • neutrophils < 1.0 x 10^9/L (unless due to FL involvement of the bone marrow) • creatinine > 1.5 times upper normal limit (unless normal creatinine clearance) • total bilirubin > 1.5 times upper normal limit (unless due to liver involvement of FL) • ALT > 2.5 times upper normal limit (unless due to liver involvement of FL) • alkaline phosphatase > 2.5 times upper normal limit (unless due to liver involvement of FL) 18) Known hypersensitivity to components of investigational product 19) Patients with pleural effusion or ascites of significant degree, defined as: a. Patients with ascites detectable by physical examination, or b. Patients with pleural effusion detectable by physical examination unless due to lymphoma involvement or recent splenectomy 20) Life expectancy less than 6 months 21) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 22) Current participation in any other interventional clinical study 23) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 24) Breast feeding women or women with a positive pregnancy test at Visit 1 25) Women of childbearing potential not willing to use adequate contraception during study and one year after last dose of HuMax-CD20. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response as measured over a 6 month period from start of treatment assessed by an Independent endpoints Review Committee (IRC) according to the standardized response criteria for Non-Hodgkin’s Lymphomas (Cheson et al.;Grillo-Lopez et al.). |
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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 | Yes |
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) | 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 | 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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 68 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 10 |