E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Hodgkin B-cell lymphoma |
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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] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Phase I part: To define MTD of Betalutin
Phase II part: To explore tumour response rates in patients receiving Betalutin |
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E.2.2 | Secondary objectives of the trial |
Phase I part: To establish recommended dose of Betalutin, investigate safety, toxicity, biodistribution, pharmacokinetic and to explore the efficacy.
Phase II part: to confirm the recommended dose of Betalutin, investigate safety and toxicity, estimate progression free survival and overall survival, quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed (by WHO classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA, marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.
2. Age ≥ 18 years.
3. A pre-study WHO performance status of 0-1.
4. Life expectancy should be ≥ 3 months.
5. <25% tumour cells in bone marrow biopsy.
6. CD37+, re-biopsy or test on existing tumour material if not known.
7. Measurable disease by radiological methods.
8. Women of childbearing potential must:
a) understand that the study medication is expected to have teratogenic risk.
b) have a negative pregnancy test.
c) agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 5 months after end of study drug therapy, even if she has amenorrhoea.
9. Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 5 months.
10. Patients previously treated with native rituximab are eligible.
11. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination.
12. The patient has been fully informed about the study and has signed the informed consent form.
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E.4 | Principal exclusion criteria |
1. Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, steroid requiring asthma/allergy, known HIV positive.
2. Laboratory values within 15 days pre-registration:
a. Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l.
b. Platelet count ≤ 150 x 109 /l.
c. Total bilirubin ≥ 30 mmol/l.
d. ALP and ALAT ≥ 4x normal level.
e. Creatinine ≥ 110 µmol/l (men), 90 µmol/l (women).
f. IgG ≤ 3 gr/l.
3. Known CNS involvement of lymphoma.
4. Previous total body irradiation, or irradiation of > 25% of the patient’s bone marrow.
5. Known history of HAMA.
6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pre-treatment with rituximab is allowed.
7. Pregnant or lactating women.
8. Previous hematopoietic stem cell transplantation (autologous and allogenic).
9. Previous treatment with radioimmunotherapy
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute – Common Terminology Criteria for Adverse Events (CTCAE version 4).
• Changes from baseline in laboratory variables: haematology and serum biochemistry.
• Changes from baseline in body temperature and vital signs (systolic/diastolic blood pressure and heart rate) during the treatment period.
• Changes from baseline in physical examination during the treatment period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline and up to 12 weeks post injection |
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E.5.2 | Secondary end point(s) |
• Incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukaemia, myelodysplastic syndrome, and aplastic anaemia).
• Overall survival.
• Estimation of whole-body retention of radioactivity at each imaging time post-injection.
• Estimation of the individual organ uptake/retention of radioactivity at each imaging time-point after injection.
• Estimate retention of administered radioactivity in blood.
• Calculation of estimated absorbed radiation dose to target organs.
• Tumour response rate.
• Tumour response duration.
• Progression-free survival
• Performance status defined as improvement or worsening, respectively, by 1-point or more on the ECOG scale from the baseline value
• Quality of life (QoL) assessed using Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline and up to 5 years post injection |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |