E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hodgkin and non-Hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Malignant lymphoma, a cancer of a subgroup of the white blood cells called lymphocytes. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025319 |
E.1.2 | Term | Lymphomas Hodgkin's disease |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025322 |
E.1.2 | Term | Lymphomas non-Hodgkin's unspecified histology |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025321 |
E.1.2 | Term | Lymphomas non-Hodgkin's T-cell |
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 |
The objective of our study is to investigate the value of the combination of 123I-MIBG and 82Rb PET/MR imaging in early detection of cardiomyopathy and prediction of HF in patients with doxorubicin-treated Hodgkin lymphoma and non-Hodgkin lymphoma. Potentially, serial 123I-MIBG and 82 Rb PET/MR scans during chemotherapy could aid in sensitive detection of cardiotoxicity and guide the modification of conventional antineoplastic regimens. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Newly diagnosed Hodgkin or non-Hodgkin lymphoma - Intended curative chemotherapeutic treatment including doxorubicin - Age > 18 years
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E.4 | Principal exclusion criteria |
- Planned mediastinal radiation therapy involving the heart (patients receiving only upper mediastinal radiation therapy can still participate) - Previous chemotherapeutic treatment - Previous mediastinal radiation therapy - Pre-existing HF of any cause (LVEF < 50%) - Significant renal disease (eGFR measured within 3 weeks prior to start of chemotherapy should be > 30ml/min/1.73 m2) - Impaired liver function (bilirubin > 20 µmol/l) - Contraindications for MR scan (severe claustrophobia, implanted metallic foreign bodies etc.) - Contraindications for PET scan (adenosine intolerance, 2nd or 3rd degree AV block, long QT syndrome, unstable angina pectoris, sinus node dysfunction) - Unwillingness to participate - Unable to give informed consent or unlikely to comply with follow-up
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E.5 End points |
E.5.1 | Primary end point(s) |
Doxorubicin-induced acute mitochondrial damage in cardiomyocytes reflected by declining coronary flow reserve measured by 82Rb PET 24-48 hours post-chemotherapy predicts the development of cardiac interstitial fibrosis measured by increase in cardiac extracellular volume (ECV) by cardiac MR at one year follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Baseline 82Rb PET/MR (prior to chemotherapy) - Acute 82Rb PET/MR (48-72 hours after the first doxorubicin-treatment) - Late MR (12-15 months post-treatment)
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E.5.2 | Secondary end point(s) |
- Doxorubicin-induced acute mitochondrial damage in cardiomyocytes reflected by declining maximal absolute myocardial perfusion measured by 82Rb PET 24-48 hours post-chemotherapy predicts the development of cardiac interstitial fibrosis measured by increase in cardiac ECV by cardiac MR at one year follow-up.
- Doxorubicin-induced subacute cardiotoxicity reflected by changes in 123I-MIBG uptake in myocardial adrenergic neurons 3 weeks post-chemotherapy predicts development of cardiac interstitial fibrosis measured by increase in cardiac ECV by cardiac MR at one year follow-up.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Baseline 82Rb PET/MR and 123I-MIBG (prior to chemotherapy) - Acute 82Rb PET/MR (48-72 hours after the first doxorubicin-treatment) - Subacute 123I-MIBG (2-3 weeks post-treatment) - Late MR (12-15 months post-treatment)
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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 | Yes |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| 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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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 | |
E.8.9.1 | In the Member State concerned days | |