Clinical trial NCT02544308: Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma
Official title: Phase III Randomised Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Plasmacytoma
Keywords: Solitary, Bone
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Celgene
First posted: 2015-09-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Primary outcomes:
measure: Progression-free survival (progression defined as development of myeloma or a new plasmacytoma outside the radiotherapy field)
timeFrame: 3 years from date of randomisation
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years from date of randomisation
measure: Time to next treatment
timeFrame: At any time during the trial (up to 6 years after last patient registered)
measure: Response to treatment
timeFrame: Approximately 1 month after Lenalidomide and Dexamethasone treatment
measure: Safety and toxicity of adjuvant lenalidomide + dexamethasone
timeFrame: During, and one month post treatment (total approximately 10 months)
measure: Surveillance for secondary malignancies
timeFrame: 5 years following treatment with lenalidomide and dexamethasone
measure: Treatment Compliance
timeFrame: 9 months from beginning of treatment
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: St James's University Hospital
name: Roger Owen
role: PRINCIPAL_INVESTIGATOR
References: