IDRIS: Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: No further treatment No further treatment |
Other: No further treatment
Comparator Arm
|
| Experimental: Lenalidomide + Dexamethasone Lenalidomide 25mg orally daily on days 1-21 Dexamethasone 20mg orally on days 1, 8, 15 & 22 Up to 9 cycles |
Drug: Lenalidomide
Experimental Arm
Other Names:
Drug: Dexamethasone
Experimental Arm
|
Outcome Measures
Primary Outcome Measures
- Progression-free survival (progression defined as development of myeloma or a new plasmacytoma outside the radiotherapy field) [3 years from date of randomisation]
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.
Secondary Outcome Measures
- Overall survival [3 years from date of randomisation]
Time from randomisation to death of any cause will be compared between arms
- Time to next treatment [At any time during the trial (up to 6 years after last patient registered)]
The time from end of radiotherapy to first date of any non-protocol treatment for plasmacytoma or myeloma will be compared between arms
- Response to treatment [Approximately 1 month after Lenalidomide and Dexamethasone 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.
- Safety and toxicity of adjuvant lenalidomide + dexamethasone [During, and one month post treatment (total approximately 10 months)]
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.
- Surveillance for secondary malignancies [5 years following treatment with lenalidomide and dexamethasone]
Second primary malignancies occurring during treatment and in the 5 years after treatment will be recorded in patients on the lenalidomide + dexamethasone arm
- Treatment Compliance [9 months from beginning of treatment]
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
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal United Hospital | Bath | United Kingdom | ||
| 2 | Blackpool Victoria Hospital | Blackpool | United Kingdom | ||
| 3 | University Hospital Wales | Cardiff | United Kingdom | ||
| 4 | Velindre Cancer Centre | Cardiff | United Kingdom | ||
| 5 | Beatson West of Scotland Cancer Centre | Glasgow | United Kingdom | ||
| 6 | St James University Hospital | Leeds | United Kingdom | ||
| 7 | University College London Hospital | London | United Kingdom | ||
| 8 | The Christie Hospital | Manchester | United Kingdom | ||
| 9 | Freeman Hospital | Newcastle | United Kingdom | ||
| 10 | Mount Vernon Cancer Centre | Northwood | United Kingdom | ||
| 11 | Royal Preston Hospital | Preston | United Kingdom | ||
| 12 | Salisbury District Hospital | Salisbury | United Kingdom | ||
| 13 | Southampton General Hospital | Southampton | United Kingdom |
Sponsors and Collaborators
- University College, London
- Cancer Research UK
- Celgene
Investigators
- Principal Investigator: Roger Owen, St James's University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UCL/13/0291