E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B cell lymphoma (DLBCL) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10012819 |
E.1.2 | Term | Diffuse large B-cell lymphomas |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 compare the biodistribution and uptake in DLBCL of 89Zirconium (89Zr)-ofatumumab and 89Zr-rituximab (visual and quantitative). |
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E.2.2 | Secondary objectives of the trial |
1. to compare the biodistribution and uptake in DLBCL of 89Zr-ofatumumab and 89Zr-rituximab with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) (visual and quantitative).
2. to quantify biodistribution and dosimetry in normal tissue of 89Zr-ofatumumab and 89Zr-rituximab.
3. to investigate whether increased uptake in DLBCL on immuno-positron emission tomography (immuno-PET) is associated with clinical efficacy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients to be included must be before initiation of second-line treatment in or conform OMB 110928 study, meeting the following criteria (conform the inclusion criteria of OMB 110928 study protocol):
Patients have refractory or relapsed (see protocol for definition) CD20 positive DLBCL during or after first line treatment with rituximab combined with anthracycline-based chemotherapy, confirmed by biopsy after first line treatment.
Age 18 years or older. Baseline 18F-FDG PET scan with positive lesions, compatible with CT defined anatomical tumor sites. CT-scan showing at least one or more clearly demarcated lesions with a largest diameter ≥ 1.5 cm or 1 clearly demarcated lesion with a largest diameter ≥ 2.0 cm (not previously irradiated). ECOG performance status 0,1 or 2. Patients must be eligible for high dose chemotherapy and autologous stem cell transplantation. Resolution of toxicities from first-line therapy to grade ≤ 1. Patients must be able to adhere to the study appointments and other protocol requirements. Patients must be capable of giving written informed consent and the consent must have been obtained prior to the study related procedures.
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E.4 | Principal exclusion criteria |
Patients are excluded if they meet the following criteria (conform the exclusion criteria of OMB 110928 study protocol):
- any previous therapy for DLBCL, with the exception of first-line treatment with rituximab in combination with anthracycline-based chemotherapy, or radiotherapy as part of the first-line treatment plan or to a limited field at a aximum dose of ≤10Gy to control life-threatening symptoms.
- received any of the following treatments within 4 weeks prior to start of trial therapy (unless otherwise stated): anti-cancer therapy, radiotherapy (unless limited field at a maximum dose of ≤ 10Gy to control life-threatening symptoms), treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrolment (whichever is longer) or currently participating in any other interventional clinical study, glucocorticoid use, unless given in doses ≤100 mg/day hydrocortisone (or equivalent dose of other glucocorticoids) for < 7 days for exacerbations other than lymphoma (e.g. asthma).
- Significant cerebrovascular disease.
- Chronic or active infections with systemic treatment with antibiotics, antifungal or antiviral medication.
- Other malignancy.
- Prior treatment with monoclonal antibodies, with the exception of rituximab, within 3 months prior to start of the study.
- Pregnancy or lactation
- Women of childbearing potential or male subjects, unable or unwilling to adhere to the adequate contraception conform study protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
1.The detection of 89Zr-ofatumumab and 89Zr-rituximab in DLBCL tumor lesions:
• visual (present/absent).
• quantitative (measured in peak Standardized Uptake Value (SUVpeak)).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Immuno-PET scans obtained 1 hour, 72 hours and 144 hours post injection of 89Zirconium-ofatumumab or 89Zirconium-rituximab. |
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E.5.2 | Secondary end point(s) |
1. The detection of 18F-FDG in DLBCL tumor lesions:
• visual (present/absent)
• quantitative (in SUVpreak).
2. The detection of 89Zr-ofatumumab and 89Zr-rituximab in normal tissue:
• visual: description of biodistribution
• quantitative (% uptake (of total injected) 89Zr-ofatumumab and 89Zr-rituximab, calculated residence times and calculated organ absorbed doses for 89Zr-ofatumumab and 89Zr-rituximab)
3. Clinical outcome:
• in categories: complete remission, partial remission, stable disease or relapsed/progressive disease, using the Revised Response Criteria for Malignant Lymphoma (RRMCML) for disease assessment, assessed by CT after the second cycle of therapy / by PET performed after the third cycle of therapy, conform OMB110928 study protocol.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immuno-PET scans obtained 1 hour, 72 hours and 144 hours post injection of 89Zirconium-ofatumumab or 89Zirconium-rituximab.
CT after the second cycle of therapy / by PET performed after the third cycle of therapy, conform OMB110928 study protocol.
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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 | No |
E.6.4 | Safety | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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The end of the study is defined as the last patients clinical follow-up parameter as used in this pilot study (CT scan after the second cycle of salvage therapy / 18F-FDG PET after the third cycle of salvage therapy). |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |