Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma

The purpose of the trial is to establish whether adjuvant therapy with lenalidomide + dexamethasone after radiotherapy can improve progression free survival in patients with high risk solitary bone plasmacytoma compared with RT only.

Solitary bone plasmacytoma (SBP) is a localised proliferation of malignant plasma cells (PCs) in the skeleton. The annual UK incidence is 0.4/100,000 (lower than multiple myeloma (MM)) with a peak age incidence at 68 years and there are estimated to be about 260 new cases per year in the United Kingdom (UK). The majority of patients with SBP ultimately progress to myeloma and this is likely due to occult disease not detected by conventional staging methods. Standard care for these patients is involved field radiotherapy (IFRT), but despite radical doses, two-thirds develop multiple myeloma at a median of 2 years, more so if there are high risk features.

The IDRIS Trial is a phase III study where the investigators hope to demonstrate that adjuvant lenalidomide + dexamethasone following IFRT prevents the development of multiple myeloma in patients with high risk solitary bone plasmacytoma. Whilst a proportion of solitary bone plasmacytoma is cured with IFRT, it is clear that the majority will progress to multiple myeloma. The investigators are seeking to prevent this outcome by using adjuvant therapy in this study.

Eligibility Criteria:
Inclusion Criteria:

* Patients with newly-diagnosed SBP
* SBP treated with local radiotherapy with curative intent (see appendix 2).
* Radiotherapy completed within 28 days of registration
* Age ≥18 years
* ECOG performance status 0-2
* Written informed consent
* Willing to comply with the requirements of the Celgene pregnancy prevention programme

Exclusion Criteria:

* Multifocal plasmacytoma, solitary extramedullary plasmacytoma or myeloma
* ≥10% bone marrow plasma cells
* Clinical suspicion of failure to respond to radiotherapy
* Receiving or intention to treat with systemic corticosteroid therapy (e.g. dexamethasone or prednisolone) unless otherwise agreed by the TMG
* Severe hepatic impairment (bilirubin \>2xULN or AST/ALT \>2xULN)
* Creatinine clearance \< 30 mL/min
* Pregnant or lactating women
* Non-haematological malignancy within the past 3 years (exceptions apply - see section 6.2.2)
* Patients at a high risk of venous thromboembolism due to:
* Treatment with erythropoietic stimulating agents (e.g. erythropoietin, epoetin alpha, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta)
* Other risk factors not listed above and unable to receive thromboprophylaxis
* Patients with untreated osteoporosis
* Patients with uncontrolled diabetes
* Patients with a known history of glaucoma
* Any other medical or psychiatric condition likely to interfere with study participation
* 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 at least 4 weeks before planned start of lenalidomide and dexamethasone.
* Evidence of current or past hepatitis B infection. Patient should test negative for both surface antigen (HBsAg) and hepatitis B core antibody (HBcAb)