Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase III Randomised Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma

Conditions
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Plasmacytoma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Dexamethasone
* Other: No further treatment


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No further treatment<br>No further treatment | Other: No further treatment<br>* Comparator Arm<br>|
| Experimental: Lenalidomide + Dexamethasone<br>Lenalidomide 25mg orally daily on days 1-21 Dexamethasone 20mg orally on days 1, 8, 15 & 22 Up to 9 cycles | Drug: Lenalidomide<br>* Experimental Arm<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Experimental Arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (progression defined as development of myeloma or a new plasmacytoma outside the radiotherapy field) | Progression free survival rate and will be analysed using Kaplan-Meier survival analysis. PSF time will be measured from date of randomisation until progression or death. | 3 years from date of randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from randomisation to death of any cause will be compared between arms | 3 years from date of randomisation | 
| Time to next treatment | The time from end of radiotherapy to first date of any non-protocol treatment for plasmacytoma or myeloma will be compared between arms | At any time during the trial (up to 6 years after last patient registered) | 
| Response to treatment | The number and proportion of patients on the lenalidomide + dexamethasone arm who achieve normalisation of the SFLCr and/or the disappearance of aberrant plasma cell phenotype following Lenalidomide + Dexamethasone treatment will be documented. | Approximately 1 month after Lenalidomide and Dexamethasone treatment | 
| Safety and toxicity of adjuvant lenalidomide + dexamethasone | During treatment and follow up, the frequency and percentages of adverse events with a maximum severity of grade 3-5 (according to CTCAE v4.03) will be collected. | During, and one month post treatment (total approximately 10 months) | 
| Surveillance for secondary malignancies | Second primary malignancies occurring during treatment and in the 5 years after treatment will be recorded in patients on the lenalidomide + dexamethasone arm | 5 years following treatment with lenalidomide and dexamethasone | 
| Treatment Compliance | Compliance with lenalidomide and dexamethasone treatment will be assessed using descriptive statistics. The number of reductions, delays and omissions of lenalidomide and dexamethasone will be presented as well as the median time on study treatment | 9 months from beginning of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solitary, Bone