E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Linfoma de células B grandes difuso
Diffuse Large B-Cell Lymphoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012821 |
E.1.2 | Term | Diffuse large B-cell lymphoma recurrent |
|
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 investigate the efficacy of ofatumumab in patients with relapsed DLBCL ineligible for transplant or relapsed after autologous transplant |
|
E.2.2 | Secondary objectives of the trial |
To determine the safety and pharmacokinetic (PK) profile of ofatumumab in patients with relapsed DLBCL ineligible for transplant or relapsed after autologous transplant |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with relapsed DLBCL and ineligible for stem cell transplantation or relapsed DLBCL after autologous stem cell transplantation 2. Tumor verified to be CD20+ positive from excisional or incisional lymph node biopsy. 3. 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 4. ECOG Performance Status of 0, 1, or 2 5. Age ≥ 18 years 6. Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out |
|
E.4 | Principal exclusion criteria |
1. More than 1 previous radioimmunotherapy regimen 2. Received radioimmunotherapy within 3 months prior to Visit 2 3. Received any of the following treatments within 4 weeks prior to Visit 2: a. Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues) b. Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day 4. Received monoclonal antibodies, other than rituximab, within 3 months prior to Visit 2 5. Patients previously treated with other anti-CD20 monoclonal antibodies than rituximab, tositumomab and ibritumomab tiuxetan (the latter two in accordance with exclusion criteria no.1 and 2) 6. Patients with previously diagnosed and treated indolent lymphoma 7. Known CNS involvement of DLBCL 8. Past or current malignancy, except for: a. Cervical carcinoma Stage 1B or less b. Non-invasive basal cell and/or squamous cell skin carcinoma c. Malignant melanoma with a complete response of a duration of < 10 years d. Other cancer diagnoses with a complete response of a duration of < 5 years 9. 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 10. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure (NYHA III-IV), and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities 11. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 12. History of significant cerebrovascular disease 13. Known HIV positive 14. Positive serology for hepatitis B (HB) defined as: a. Positive test for HBsAg and/or b. Positive test for anti-HBs and anti-HBc Patients with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will not be considered positive.
15. Screening laboratory values: a. platelets < 50 x 10^9/L (unless due to DLBCL involvement of the bone marrow) b. neutrophils < 1.0 x 10^9/L (unless due to DLBCL involvement of the bone marrow) c. creatinine > 2.0 times upper normal limit (unless normal creatinine clearance) d. total bilirubin > 1.5 times upper normal limit (unless due to liver involvement of DLBCL) e. ALT > 2.5 times upper normal limit (unless due to liver involvement of DLBCL) f. alkaline phosphatase > 2.5 times upper normal limit (unless due to liver involvement of DLBCL) 16. Known or suspected hypersensitivity to components of investigational product 17. Life expectancy less than 6 months 18. Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 19. Current participation in any other interventional clinical trial 20. Patients known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 21. Breast feeding women or women with a positive pregnancy test at Visit 1 22. Women of childbearing potential not willing to use adequate contraception during trial and one year after last dose of ofatumumab. 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response as measured over a 6 month period from start of treatment with ofatumumab assessed according to the “Revised response criteria for malignant lymphoma" |
|
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) | 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 | 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) | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
|
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
|
Last visit of last patient |
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 9 |