E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Richter’s Syndrome; a high-grade transformation that occurs in 5-15% of patients with B cell chronic lymphocytic leukaemia (B-CLL). |
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MedDRA Classification |
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 |
The primary objective is to determine objective response to ofatumumab plus CHOP at week 13, week 20 and week 72 as measured from start of treatment according to the Revised Response Criteria for Malignant Lymphoma. In other words, the purpose of the trial is to find out if the addition of Ofatumumab to standard chemotherapy treatment is better (more patients living longer) than the standard chemotherapy alone. |
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E.2.2 | Secondary objectives of the trial |
To assess feasibility of recruitment. To further assess the efficacy of CHOP in combination with Ofatumumab in induction and maintenance treatment of Richter’s Syndrome. To assess the safety and tolerability of CHOP in combination with Ofatumumab in induction and maintenance treatment of Richter’s Syndrome, i.e. are there any rare side effects of Ofatumumab in combination with chemotherapy that we do not know about? To validate potential candidate risk factors in peripheral blood and lymph nodes that may be associated with the development of Richter’s transformation. To identify novel drivers of transformation and predictors of response to treatment. To assess the clinical benefit and changes in patient reported outcome measures (PRO). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed written informed consent prior to performing any study-specific procedures 2) Patients with B-CLL and newly diagnosed not previously treated and biopsy proven DLBCL Richter’s transformation 3) ECOG Performance Status of 0, 1, 2 or 3 4) Age 18 years and over. |
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E.4 | Principal exclusion criteria |
1) Treatment for DLBCL within 6 months prior to Visit 1 2) Known CNS involvement of B-CLL 3) Any malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma 4) 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. Subjects meeting any of the following criteria must not be enrolled in the study: Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded 5) Clinically significant cardiac disease including unstable angina, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities 6) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 7) History of significant cerebrovascular disease in last 6 months 8) Known HIV positive 10) Known or suspected hypersensitivity to components of investigational product 11) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 12) Current participation in any other interventional clinical study 13) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 14) Breast feeding women or women with a positive pregnancy test at Visit 1 15) Women of childbearing potential not willing to use adequate contraception during study and for two months after last dose of Ofatumumab. Adequate contraception is defined as abstinence, hormonal birth control or intrauterine devices. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is overall response rate to CHOP-O as defined by the revised response criteria for malignant lymphoma (Cheson et al, JCO, Vol 25, No 5, p579-586 2007). Patients will be classified as responders/non-responders as follows: complete remission, nodular partial remission and partial remission are classified as responders; while stable disease and progressive disease are classified as non-responders. Non-evaluable patients will be classified as non-responders. |
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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 | 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 | 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 | No |
E.8.1.7.1 | Other trial design description |
Multi-centre non-randomised feasibility study |
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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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 5 |
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 | 5 |