MUK Nine b: OPTIMUM Treatment Protocol (MUKnineb)
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|ClinicalTrials.gov Identifier: NCT03188172|
Recruitment Status : Recruiting
First Posted : June 15, 2017
Last Update Posted : April 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Cyclophosphamide Drug: Bortezomib Drug: Lenalidomide Drug: Daratumumab Drug: Dexamethasone Drug: Melphalan Drug: Filgrastim||Phase 2|
Multiple myeloma (MM) is a plasma cell tumour with an annual incidence in the UK of approximately 40 -50 per million i.e. 4500 new cases per annum. Approximately 20% of the patients diagnosed with multiple myeloma have a significantly worse prognosis at 3 years than other multiple myeloma patients and these are characterised as having high risk (HR) disease defined by genetic lesions and gene expression profiles (GEP). There have been no significant improvements in outcome over the last decade for patients with HR disease. Therefore, it is important to identify more effective treatment options for this group of patients especially given that the number of novel agents are potentially available and which can be given as part of intensive therapy regimen.
Intensive treatment in HR patients has been used outside the UK with promising results but access to drugs in the UK has been challenging with constraints in the NHS treatment pathway. This is the first time in the UK that newly diagnosed multiple myeloma patients may be entered into a clinical trial prospectively according to their genetic risk profile. It provides a unique opportunity to improve outcomes and provide evidence for high cost novel treatment strategies in this restricted population of poor prognosis patients.
The MUKnine trial is designed to evaluate the novel treatment strategies for multiple myeloma patients with HR disease and incorporate a genetic screening component. Patients identified as having HR disease are then invited to take part in the phase II single arm, multi centre trial that investigates the intensive treatment schedule comprising four novel agents bortezomib (Velcade), lenalidomide (Revlimid), daratumumab (Daralex), dexamethasone with cyclophosphamide. The trial will determine if this treatment strategy is sufficiently active to take forward in to further testing in this population. Patients identified as not having HR disease will receive standard local treatment and will be followed up in a cohort study to assess response, progression free survival and overall survival.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||95 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The trial is designed as a single arm phase II trial with interim assessments for futility, using a Bayesian strategy for monitoring multiple outcomes.|
|Masking:||None (Open Label)|
|Official Title:||MUK Nine b: OPTIMUM. A Phase II Study Evaluating Optimised Combination of Biological Therapy in Newly Diagnosed High Risk Multiple Myeloma and Plasma Cell Leukaemia.|
|Actual Study Start Date :||September 28, 2017|
|Estimated Primary Completion Date :||October 1, 2020|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Trial Treatment
Cyclophosphamide 500mg, days 1, 8 Bortezomib 1.3mg/m2, days 1, 4, 8, 11 Lenalidomide 25mg, days 1-14 Daratumumab 16mg/kg, days 1, 8, 15 (cycles 1& 2), day 1 only from cycle 3 Dexamethasone 20-40mg, days 1, 4, 8, 11
ASCT stem cell harvest:
with Bortezomib 1.3mg/m2, (12 hours post melphalan) Bortezomib 1.3mg/m2, day +5, +14, weekly
Consolidation part 1:
Bortezomib 1.3mg/m2 days 1, 8, 15, 22 Lenalidomide 25mg days 1-21 Daratumumab 16mg/kg day 1 Dexamethasone 20-40mg days 1, 8, 15, 22
Consolidation part 2:
Bortezomib 1.3mg/m2 days 1, 8, 15 Lenalidomide 25mg days 1-21 Daratumumab 16mg/kg day 1
Lenalidomide 10mg days 1-21 Daratumumab 16mg/kg day 1
Other Name: Velcade
Other Name: Revlamid
Other Name: Daralex
Haematopoietic agent for the stem cell harvest
- Progression free survival [ Time Frame: At 18 months post registration ]Defined as the time from registration until first documented evidence of progressive disease or death. Participants not progressed at analysis will be censored at the last date known to be alive and progression free.
- Occurrence of Serious Adverse Events(SAE) and Suspected, Unexpected Serious Adverse Reactions (SUSAR) [ Time Frame: At 120 days post autologous stem cell transplant (ASCT) ]Will be reported based on occurrence of SAE & SUSARs with details of causality and expectedness.
- Progression free survival at 100 days post autologous stem cell transplant [ Time Frame: At 100 days post ASCT ]Determine whether the treatment schedule should be dropped for futility
- Minimal residual disease (MRD) negative disease [ Time Frame: At 100 days post ASCT ]Defined as absence of aberrant phenotype plasma cells
- Overall survival [ Time Frame: At 12 months, 24 months & 36 months post registration ]Median overall survival estimates
- Maximum response [ Time Frame: From registration to end of induction therapy, 100 days post ASCT, post consolidation part 2 ]Proportion of participants achieving each response category. Time from registration until the participant achieves a maximum response.
- Overall response [ Time Frame: At end of induction therapy, 100 days post ASCT, post consolidation part 2 ]Proportion of participants receiving at least a partial response
- Second progression free survival [ Time Frame: From registration until second disease progression, 3 years ]Time from registration to second disease progression or death.
- Overall treatment benefit [ Time Frame: At the end of induction therapy and 100 days post autologous stem cell transplant ]Clinician assessment of treatment benefit will be obtained
- Quality of Life [ Time Frame: From registration until second disease progression, 3 years ]Based on EQ-5D outcome measure combined with EORTC QLQ-C30 and MY20 responses
- Progression free survival (comparison with Myeloma XI/XI+ data) [ Time Frame: From registration until second disease progression, 3 years ]Matched comparison of progression free survival
- Impact of minimal residual disease on progression free survival [ Time Frame: From registration until second disease progression, 3 years ]Analysis will include any participant with a MRD assessment
- Genomic instability [ Time Frame: From registration until second disease progression, 3 years ]To be investigated in an exploratory manner and will include analysis of new genetic abnormalities
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03188172
|Contact: Debbie Sherratt||0113 email@example.com|
|Principal Investigator:||Martin Kaiser||University of Leeds|