| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Solitary bone plasmacytoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Build up of abnormal plasma cells at a single place in the skeleton |
|
| 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 | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10035484 |
| E.1.2 | Term | Plasmacytoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 investigate whether the administration of adjuvant lenalidomide and dexamethasone following standard radiotherapy treatment for solitary bone plasmacytoma prevents or prolongs the time to development of further plasmacytomas or progression to myeloma, or death (whichever comes first), in patients with high-risk disease compared with RT only. |
|
| E.2.2 | Secondary objectives of the trial |
To investigate whether administration of adjuvant lenalidomide and dexamethasone following standard radiotherapy treatment for solitary bone plasmacytoma results in the eradication of occult marrow disease and normalisation of previously abnormal serum free light chain ratios;
To compare the time to next treatment for plasmacytoma in patients with high risk features who receive lenalidomide and dexamethasone and those who do not.
To investigate whether there is a difference in overall survival between patients who receive adjuvant lenalidomide and dexamethasone, and those who do not;
To investigate the safety and toxicity of adjuvant lenalidomide and dexamethasone in solitary bone plasmacytoma patients, in particular rates of second primary malignancies;
To compare the impact of lenalidomide and dexamethasone or a watch and wait strategy on quality of life. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
INCLUSION CRITERIA FOR REGISTRATION:
1. Patients with newly-diagnosed SBP as defined by IMWG and BCSH guidelines that has been confirmed histologically
2. Treated or being treated with local radiotherapy as per BCSH guidelines
3. Age ≥18 years
4. ECOG performance status 0-2
5. Written informed consent
6. Willing to comply with the requirements of the Celgene pregnancy prevention programme
INCLUSION CRITERIA FOR RANDOMISATION:
1. Patients who have one or both of the high risk features will be eligible for randomisation:
- Phenotypically aberrant plasma cells in a BM aspirate taken from a site outside the radiotherapy field and/or
- Abnormal serum free light chain ratio at diagnosis or the next possible time point if not collected at diagnosis (determined by local reference ranges)
|
|
| E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA FOR REGISTRATION:
1. Multifocal plasmacytoma, solitary extramedullary plasmacytoma or myeloma
2. ≥10% bone marrow plasma cells
3. On, or planned for, systemic steroid therapy (e.g. dexamethasone or prednisolone) unless otherwise agreed by the TMG
4. Severe hepatic impairment (bilirubin >2xULN or AST/ALT >2xULN)
5. Creatinine clearance <30mL/min
6. Pregnant or lactating women
7. Non-haematological malignancy within the past 3 years (exceptions apply – see section 6.2.2)
8. Patients at a high risk of venous thromboembolism due to:
-Treatment with erythropoietic stimulating agents (e.g. erythropoetin, epoetin alpha, neo- recormon, aranesp)
-Other risk factors not listed above
9. Patients with untreated osteoporosis
10. Patients with uncontrolled diabetes
11. Patients with glaucoma
12. Any other medical or psychiatric condition likely to interfere with study participation
13. Receiving treatment with an experimental drug or experimental medical device. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. Any experimental drug treatments must be stopped within 4 weeks of planned start of lenalidomide and dexamethasone.
14. Evidence of current or past hepatitis B infection.
15. Uncontrolled active systemic infection.
EXCLUSION CRITERIA FOR RANDOMISATION:
1. Receiving or intention to treat with systemic corticosteroid therapy (e.g. Dexamethasone) unless otherwise agreed by the TMG. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival (progression-free survival defined as time from randomisation until development of myeloma or a new plasmacytoma outside the radiotherapy field, or death, whichever happens first) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| End of treatment, follow up visits (years 1 & 2: 3 monthly, years 3-5: 6 monthly and annually thereafter). |
|
| E.5.2 | Secondary end point(s) |
1. Proportion of patients treated with Lenalidomide and Dexamethasone who eradicate occult marrow disease as determined by multiparameter flow cytometry.
2. Proportion of patients treated with lenalidomide and Dexamethasone who achieve normalisation of the serum free light chain (SFLC) ratio
3. Time to next treatment
4. Overall survival
5. Safety and toxicity of adjuvant lenalidomide + dexamethasone
6. Surveillance of secondary malignancies in the 5 years following treatment with lenalidomide + dexamethasone
7. Treatment compliance
8. Quality of life |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 1 month after completion of lenalidomide and dexamethasone
2. 1 month after completion of lenalidomide and dexamethasone
3. Follow up visits (years 1&2: 3-monthly, years 3-5: 6-monthly, annually thereafter)
4. End of treatment, follow up visits as detailed above, and long term flagging with HSCIC.
5. Adverse event assessment at day 1 of each cycle and follow up visits as detailed above until 28 days post completion of lenalidomide and dexamethasone.
6. Follow up visits as detailed above, and long term flagging with HSCIC
7. At the completion of each cycle of adjuvant lenalidomide and dexamethasone, end of all treatment
8. Randomisation, then every 3 months from the date of completion of radiotherapy for 2 years
|
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Standard care - No treatment |
|
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 35 |
| 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 | 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
|
For regulatory purposes the end of trial will be the last patient's last visit to address the trial endpoints, at which point the 'declaration of end of trial' form will be submitted to participating regulatory authorities and ethical committees, as required.
Following this, UCL CTC will advise sites on the procedure for closing the trial at site level. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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