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Multiple MyelomaPhase 2MUKninebNCT03188172

MUK Nine b: OPTIMUM Treatment Protocol

A Phase 2 study testing Cyclophosphamide, Bortezomib and Lenalidomide in people with Multiple Myeloma, run by University of Leeds at 21 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To determine whether a combination of four novel agents bortezomib(Velcade), lenalidomide (Revlimid), Daratumumab (Darzalex) \& dexamethasone in combination with low-dose cyclophosphamide is sufficiently active in a high risk population of myeloma patients, to take forward into a phase III trial compared to standard… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Cyclophosphamide, Bortezomib and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
21 sitesUnited Kingdom
Study dates
28 Sep 2017to 31 May 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmation of High Risk status from Institute of Cancer Research (ICR) following bone marrow and blood sample processed through the MUKnine a screening protocol.
  • Previously untreated participants, although participants may have received up to 2 cycles of cyclophosphamide, thalidomide, dexamethasone (CTD), cyclophosphamide, velcade, dexamethasone (CVD), cyclophosphamide, lenalidomide, dexamethasone (CRD) or velcade, thalidomide, dexamethasone (VTD) pre-trial induction chemotherapy while awaiting the results of the laboratory analysis from the MUKnine a Screening Protocol. (In addition, non-systemic therapy such as therapeutic plasma exchange, dexamethasone up to a maximum of 160mg or radiotherapy sufficient to alleviate or control pain or local invasion is permitted).
  • Measurable disease with at least one of the following or willing to undergo further bone marrows for assessment:
  • Paraprotein ≥ 5g/L or ≥ 0.5 g/L for IgD subtypes.
  • Serum free kappa or lambda light chains ≥ 100 mg/L with abnormal ratio (for light chain only myeloma).
  • Urinary Bence Jones protein ≥ 200 mg/L.
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  • Non measurable participants providing they accept a 3 monthly bone marrow during induction and a 6 monthly bone marrow assessment during consolidation and maintenance.
  • Aged 18 years or over.
  • Fit for intensive chemotherapy and autologous stem cell transplant (at clinician's discretion).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
  • The Celgene Pregnancy Prevention Plan must be followed and participants must agree to comply with this:
  • Females of childbearing potential (FCBP) must agree to utilise two reliable forms of contraception simultaneously or practice complete abstinence for at least for 28 days prior to starting trial treatment, during the trial and for at least 28 days after trial treatment discontinuation, and even in case of dose interruption, and must agree to regular pregnancy testing during this timeframe.
  • Males must agree to use a latex condom during any sexual contact with FCBP during the trial, including during dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy o Males must also agree to refrain from donating semen or sperm while on trial treatment including during any dose interruptions and for at least 6 months after discontinuation from this trial
  • All participants must agree to refrain from donating blood while on trial drug including during dose interruptions and for 28 days after discontinuation from this trial.
  • Calculated creatinine clearance ≥ 30mL/min (using Cockcroft-Gault formula).
  • Alanine transaminase (ALT) and/or Aspartate transaminase (AST) ≤ 2.5 times upper limit of normal (ULN).
  • Bilirubin ≤ 2.0 x ULN, except in participants with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin ≤2.0 times ULN
  • Platelet count ≥ 75 x 109/L. (≥ 50 x 109/L if myeloma involvement in the bone marrow is >50%). Platelet support is permitted.
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L. Growth factor support is permitted.
  • Haemoglobin ≥ 80 g/L. (Participants may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines.
  • Corrected serum calcium ≤ 3.5 mmol/L.
  • Minimum stem cell harvest of 2 x 106 CD34+ cells/kg body weight.
  • Received a minimum of 4, unless a complete response (CR) has been achieved with a lesser number, or a maximum of 6 Induction (CVRDd) cycles.
  • Achieved a response of stable disease (SD) or better.
  • Exclusion Criteria for ASCT 1. Participants that have progressive disease.
  • Undergone autologous transplant with high dose melphalan-velcade (HDM-V) conditioning (Participants must have received a minimum of 100 mg/m2 Melphalan in order to proceed with consolidation).
  • Neutrophils ≥ 1.0 x 109/L. Growth factor support is permitted.
  • Platelet count ≥ 75 x 109/L. Platelet support is permitted.
  • Received 6 cycles of Consolidation Part 1 (VRDd) or 1 cycle of VRd pre-harvest plus 5 cycles of Consolidation Part 1 (VRDd).
  • Neutrophils ≥ 1.0 x 109/L. Growth factor support is permitted.
  • Platelet count ≥ 75 x 109/L. Platelet support is permitted.
  • Received 12 cycles of Consolidation Part 2 (VRD).
  • Neutrophils ≥ 1.0 x 109/L. Growth factor support is permitted.
  • Platelet count ≥ 75 x 109/L. Platelet support is permitted.

Who cannot join

  • Solitary bone/solitary extramedullary plasmacytoma.
  • Primary diagnosis of amyloidosis, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma or Waldenstrom's Disease.
  • Prior or concurrent invasive malignancies except the following:
  • Adequately treated basal cell or squamous cell skin cancer.
  • Incidental finding of low grade (Gleason 3+3 or less) prostate cancer.
  • Any cancer from which the subject has been disease free for at least 3 years.
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  • Known/underlying medical conditions that, in the investigator's opinion, would make the administration of the study drug hazardous (e.g. uncontrolled diabetes or uncontrolled coronary artery disease).
  • Any clinically significant cardiac disease, including:
  • myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV.
  • Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4 Grade ≥2) or clinically significant ECG abnormalities.
  • screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec. · Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed). Participants with known or suspected COPD or asthma must have a FEV1 test during screening.
  • Known to be seropositive for history of human immunodeficiency virus (HIV) or known to have active hepatitis B or hepatitis C.
  • Any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts), or known sensitivity to mammalian-derived products.
  • Clinically significant allergies or intolerance to cyclophosphamide, lenalidomide, velcade, daratumumab or dexamethasone. · Previous treatment with daratumumab or any other anti-CD38 therapies.
  • Participants with contraindication to thromboprophylaxis.
  • Grade 2 or greater peripheral neuropathy (per NCI-CTCAEv4.0).
  • Participants with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
  • Known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder). Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
  • Participant is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this trial or within at least 6 months after the last dose of trial treatment. Or, participant is a man who plans to father a child while taking part in this trial or within at least 6 months after the last dose of trial treatment.
  • Major surgery within 2 weeks before treatment protocol registration or has not fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Kyphoplasty or vertebroplasty is not considered major surgery.
  • Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before treatment protocol registration or is currently enrolled in an interventional investigational study.
  • 1. Participants that have progressive disease.
  • 1. Participants that have progressive disease.
  • 1. Participants that have progressive disease.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United Kingdom21 sites

  • Queen Elizabeth Hospital

    Birmingham, B15 2TH

  • Birmingham Heartlands Hospital

    Birmingham

  • Blackpool Victoria Hospital

    Blackpool

  • Royal Hampshire County Hospital

    Bournemouth, BH7 7DW

  • Royal Bournemouth Hospital

    Bournemouth

  • Bristol Haematology & Oncology Centre

    Bristol

  • Ninewells Hospital

    Dundee, DD1 9SY

  • Beatson Oncology Centre

    Glasgow

  • Kettering General Hosptial

    Kettering, NN16 8UZ

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

  • Kings College Hosptial

    London

  • Manchester Royal Infirmary

    Manchester

  • The Christie Hospital

    Manchester

  • Norfolk and Norwich University Hospital

    Norwich

  • Nottingham University Hosptial

    Nottingham

  • Churchill Hospital

    Oxford

  • Derriford Hospital

    Plymouth

  • Southampton General Hospital

    Southampton, SO16 6YD

  • Royal Stoke Hospital

    Stoke-on-Trent

  • Royal Marsden Hospital

    Sutton, SM2 5PT

  • Worcester Royal Hospital

    Worcester, WR5 1DD

Other trials in United Kingdom

About this study

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.

To determine whether a combination of four novel agents bortezomib(Velcade), lenalidomide (Revlimid), Daratumumab (Darzalex) \& dexamethasone in combination with low-dose cyclophosphamide is sufficiently active in a high risk population of myeloma patients, to take forward into a phase III trial compared to standard treatment.

Read the detailed description

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.

Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03188172
Study groupRoleWhat they receive
Trial TreatmentExperimentalInduction: 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 Maintenance: Lenalidomide 10mg days 1-21 Daratumumab 16mg/kg day 1
Receives: Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone; Drug: Melphalan; Drug: Filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    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.

    Measured: At 18 months post registration

Secondary outcomes (11)

  1. Occurrence of Serious Adverse Events(SAE) and Suspected, Unexpected Serious Adverse Reactions (SUSAR)

    Will be reported based on occurrence of SAE \& SUSARs with details of causality and expectedness.

    Measured: At 120 days post autologous stem cell transplant (ASCT)

  2. Progression free survival at 100 days post autologous stem cell transplant

    Determine whether the treatment schedule should be dropped for futility

    Measured: At 100 days post ASCT

  3. Minimal residual disease (MRD) negative disease

    Defined as absence of aberrant phenotype plasma cells

    Measured: At 100 days post ASCT

  4. Overall survival

    Median overall survival estimates

    Measured: At 12 months, 24 months & 36 months post registration

  5. Maximum response

    Proportion of participants achieving each response category. Time from registration until the participant achieves a maximum response.

    Measured: From registration to end of induction therapy, 100 days post ASCT, post consolidation part 2

  6. Overall response

    Proportion of participants receiving at least a partial response

    Measured: At end of induction therapy, 100 days post ASCT, post consolidation part 2

  7. Second progression free survival

    Time from registration to second disease progression or death.

    Measured: From registration until second disease progression, 3 years

  8. Overall treatment benefit

    Clinician assessment of treatment benefit will be obtained

    Measured: At the end of induction therapy and 100 days post autologous stem cell transplant

  9. Quality of life using the EQ-5D questionnaire

    Quality of life will be summarised at each post-registration timepoint, adjusting for baseline mean scores and 95% confidence intervals. This will also be summarised descriptively using bar charts, box plots, plots of mean QoL over time and summary tables.

    Measured: From registration until second disease progression, 3 years

  10. Quality of life using the EORTC QLQ-C30 questionnaire

    Quality of life will be summarised at each post-registration timepoint, adjusting for baseline mean scores and 95% confidence intervals. This will also be summarised descriptively using bar charts, box plots, plots of mean QoL over time and summary tables.

    Measured: From registration until second disease progression, 3 years

  11. Quality of life using the QLQ-MY20 questionnaire

    Quality of life will be summarised at each post-registration timepoint, adjusting for baseline mean scores and 95% confidence intervals. This will also be summarised descriptively using bar charts, box plots, plots of mean QoL over time and summary tables.

    Measured: From registration until second disease progression, 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2017
  2. Study start28 Sep 2017
  3. Primary completion1 Oct 2025 (estimated)
  4. Study completion31 May 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03188172
Sponsor's protocol ID
HM16/235
Acronym
MUKnineb
Status last verified
May 2024
First submitted
2 May 2017
Last updated
14 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kaiser MF, Phillip RH, Brown SR, Holroyd A, Ferris E, de Tute RM, Roberts S, Clayton L, Bowles K, Garg M, Lokare A, Messiou C, Houlston RS, Jackson G, Cook G, Owen RG, Drayson MT, Pratt G, Hall A, Jenner MW. Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial. Lancet Oncol. 2026 Sep 7:S1470-2045(26)00286-X. doi: 10.1016/S1470-2045(26)00286-X. Online ahead of print.

    PubMed 42705255

  • Keaveney S, Dragan A, Rata M, Blackledge M, Scurr E, Winfield JM, Shur J, Koh DM, Porta N, Candito A, King A, Rennie W, Gaba S, Suresh P, Malcolm P, Davis A, Nilak A, Shah A, Gandhi S, Albrizio M, Drury A, Pratt G, Cook G, Roberts S, Jenner M, Brown S, Kaiser M, Messiou C. Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study. Insights Imaging. 2023 Oct 15;14(1):170. doi: 10.1186/s13244-023-01498-3.

    PubMed 37840055

  • Kaiser MF, Hall A, Walker K, Sherborne A, De Tute RM, Newnham N, Roberts S, Ingleson E, Bowles K, Garg M, Lokare A, Messiou C, Houlston RS, Jackson G, Cook G, Pratt G, Owen RG, Drayson MT, Brown SR, Jenner MW. Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma. J Clin Oncol. 2023 Aug 10;41(23):3945-3955. doi: 10.1200/JCO.22.02567. Epub 2023 Jun 14.

    PubMed 37315268

  • Rata M, Blackledge M, Scurr E, Winfield J, Koh DM, Dragan A, Candito A, King A, Rennie W, Gaba S, Suresh P, Malcolm P, Davis A, Nilak A, Shah A, Gandhi S, Albrizio M, Drury A, Roberts S, Jenner M, Brown S, Kaiser M, Messiou C. Implementation of Whole-Body MRI (MY-RADS) within the OPTIMUM/MUKnine multi-centre clinical trial for patients with myeloma. Insights Imaging. 2022 Jul 28;13(1):123. doi: 10.1186/s13244-022-01253-0.

    PubMed 35900614

  • Oliva S, Kaiser MF. Is it time to tailor treatment on the basis of minimal residual disease in multiple myeloma? Lancet Haematol. 2021 Dec;8(12):e876-e877. doi: 10.1016/S2352-3026(21)00341-0. No abstract available.

    PubMed 34826409

  • Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

    PubMed 33357481

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Bortezomib and Lenalidomide in people with Multiple Myeloma, run by University of Leeds at 21 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: At 18 months post registration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03188172, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.

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MUK Nine b: OPTIMUM Treatment Protocol (NCT03188172) | AzTrials