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Relapsed or Refractory Multiple MyelomaPhase 2MUKtwelveNCT06212596

Selinexor, Cyclophosphamide and Prednisone in Myeloma

A Phase 2 study testing Selinexor, Cyclophosphamide and Prednisone in people with Relapsed or Refractory Multiple Myeloma, run by University of Leeds at 13 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The trial is designed as a randomised, controlled, open, parallel group, multi-centre phase II trial to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisone. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed or Refractory Multiple Myeloma
What is being tested?
Selinexor, Cyclophosphamide and Prednisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
13 sitesUnited Kingdom
Study dates
16 Jul 2018to 14 Nov 2023
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to give informed consent and willing to follow all trial protocol assessments
  • Aged 18 years or over
  • Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria (Rajkumar et al. (2014))
  • Measurable disease with at least one of the following:
  • Paraprotein ≥5g/L
  • Serum free light chains ≥100mg/L with abnormal ratio for light chain only myeloma
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  • Bence Jones protein ≥200mg/L
  • Participants with relapsed or relapsed refractory myeloma who have received ≥ 2 prior anti-myeloma treatments including a proteasome inhibitor and lenalidomide, and now require further treatment
  • Patients for which cyclophosphamide and prednisone alone would be a suitable treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative urine pregnancy test at screening.
  • Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
  • For both male and female participants, effective methods of contraception must be used throughout the trial and for at least 36 months following the last dose of trial treatment
  • Required laboratory values within 14 days prior to randomisation:
  • Platelet count ≥50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
  • Absolute neutrophil count ≥1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
  • Haemoglobin ≥ 8090 g/L. Blood support is permitted
  • Alanine transaminase (ALT) and / or aspartate transaminase (AST) ≤3 x upper limit of normal
  • Creatinine clearance ≥ 2030 ml/min (using Cockcroft Gault formula)
  • Bilirubin ≤1.5 x upper limit of normal . Gilberts syndrome patients must have a total bilirubin ≤3 x upper limit of normal

Who cannot join

  • The following participants will be excluded:
  • those with non-measurable disease
  • those with a solitary bone or solitary extramedullary plasmacytoma
  • plasma cell leukaemia
  • Participants with a history of malignancy (other than myeloma) within 5 years before the date of randomisation (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that, in the opinion of the investigator, with concurrence with the Chief Investigator, is considered cured with minimal risk of recurrence within 5 years)
  • Participants with a known or underlying uncontrolled concurrent illness that, in the investigator's opinion, would make the administration of the trial drug hazardous or circumstances that could limit compliance with the trial, including, but not limited to the following:
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  • acute or chronic graft versus host disease
  • uncontrolled hypertension
  • symptomatic congestive heart failure
  • unstable angina pectoris
  • myocardial infarction within past 6 months
  • uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4 GradeCTCAE grade ≥2)
  • active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
  • psychiatric or social conditions that may interfere with participant compliance
  • uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
  • or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the participant at unacceptable risk for adverse outcome if he/she were to participate in the trial
  • Participants who have previously received Selinexor or any other SINE compound
  • Previous anti-tumour therapies including investigational medicinal products at any dose within 28 days before the start of protocol treatment.
  • Prednisone up to a dose of 175 mg per week may be given between screening and the beginning of treatment if medically required but should be stopped before trial treatment starts.
  • Bisphosphonates for bone disease are also permitted
  • Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures or conditions that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the trial drug(s)
  • Peripheral neuropathy of CTCAE grade ≥ grade 32 (or ≥ grade 21 with pain) severity (as per NCI-CTCAEv4.0 )
  • Female participants who are lactating or have a positive pregnancy test at screening
  • Known allergy or previous intolerance to any of the trial medications, their analogues, or excipients in the various formulations of any agent that would prevent the participant receiving these as directed in the protocol
  • Major surgery within 14 days prior to randomisation
  • Radiotherapy within 7 days prior to randomisation for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation
  • Chemotherapy or immunotherapy or any other anticancer therapy within 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1 (NB: except steroids in the doses outlined above)
  • Myeloma involving the Central Nervous System
  • SCP following CP Inclusion Criteria
  • Randomised to CP on the MUKtwelve trial, has tolerated treatment and can continue on CP during the SCP treatment, and received at least one full cycle of treatment
  • Centrally confirmed disease progression by IMWG criteria. This must be confirmed by two consecutive assessments based on local lab results. Local laboratory reports must be sent to CTRU to confirm progression and site must have received confirmation of progression from CTRU.
  • ECOG performance status ≤2
  • Required laboratory values within 14 days prior to starting treatment on SCP:
  • Platelet count ≥50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to starting SCP, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
  • Absolute neutrophil count ≥1.0 x 109/L.
  • Haemoglobin ≥ 80 g/L. Blood support is permitted
  • Alanine transaminase (ALT) and / or aspartate transaminase (AST) ≤3 x upper limit of normal
  • Creatinine clearance ≥ 20 ml/min (using Cockcroft Gault formula)
  • Bilirubin ≤1.5 x upper limit of normal. Suspected Gilberts syndrome patients must have a total bilirubin ≤3 x upper limit of normal
  • B2M
  • Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative urine pregnancy test at screening.
  • Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
  • For both male and female participants, effective methods of contraception must be used throughout the trial and for 12 months following the last dose of trial treatment

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United Kingdom13 sites

  • Birmingham Heartlands Hospital

    Birmingham

  • Royal Bournemouth Hospital

    Bournemouth

  • Leicester Royal Infirmary

    Leicester

  • Royal Liverpool University Hospital

    Liverpool

  • St Bartholomew Hospital

    London, EC1M 6BQ

  • Guys and St Thomas NHS Foundation Trust

    London, SE1 9RT

  • Imperial College Healthcare NHS Trust

    London, W2 1NY

  • Royal Marsden Hospital

    London

  • James Cook University Hospital

    Middlesbrough

  • Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital

    Sheffield

  • University Hospital Southampton

    Southampton, SO16 6YD

  • Royal Stoke University Hospital

    Stoke-on-Trent

  • Worthing Hospital

    Worthing

Other trials in United Kingdom

About this study

Official title: A Randomised Phase II Trial of Selinexor, Cyclophosphamide and Prednisone vs Cyclophosphamide and Prednisone in Relapsed or Refractory Multiple Myeloma (RRMM) Patients

The trial is designed as a randomised, controlled, open, parallel group, multi-centre phase II trial to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisone.

Read the detailed description

The trial is designed as a randomised, controlled, open, parallel group, multi-centre phase II trial to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisone. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE). Selinexor forms slowly reversible adducts with the substrate binding pocket of Exportin and has been demonstrated to lead to effective cell kill by causing accumulation pro-apoptotic proteins in the nucleus of myeloma cells. To maximise response to this novel drug in a relapsed-refractory setting, Selinexor will be combined with low-dose cyclophosphamide and prednisone. Lower, continuous doses of cyclophosphamide and intermittent doses of prednisone have been chosen to limit toxicity for the triplet regimen in the elderly myeloma patient population. A calibration group will receive cyclophosphamide plus prednisone alone, and will be used to evaluate the validity of the outcome in the experimental group.

Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisone (SCP) or cyclophosphamide + prednisone (CP).

A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 participants in the CP arm).

Participants who experience disease progression on the CP arm, may receive SCP, once progression has been confirmed by the CTRU and the participant has been deemed eligible to receive SCP. Patients randomised to SCP have no further trial treatment stipulated following SCP therapy. The analysis of the treatment switch phase of the trial is exploratory.

Participants will be recruited from approximately 10 NHS Hospitals throughout the UK.

Being tested
Selinexor, Cyclophosphamide, Prednisone
Keywords
Myeloma
Medical subject headings
Recurrence, Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

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

  • SelinexorDrug

    Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumour suppressor proteins (TSPs). Selinexor is an oral, first-in-class, potent, slowly reversible, covalent-binding Selective Inhibitor of Nuclear Export (SINE) compound that specifically blocks the karyopherin protein Exportin 1 (XPO1), also called chromosome region maintenance 1.

  • CyclophosphamideDrug

    Cyclophosphamide is a long used conventional chemotherapy with potent anti-myeloma activity and low toxicity when administered at low doses as in the current protocol (Hajek et al. (2016)). It is being extensively used in combination with novel agents, including bortezomib, lenalidomide, and pomalidomide, and provides a cost-effective and well-tolerated alternative as a combination partner (Morgan et al. (2007); Mai et al. (2015); Baz et al. (2016)).

  • PrednisoneDrug

    Steroids have been a very effective backbone for every myeloma combination therapy developed so far. Prednisone is the standard steroid in a number of widely used regimens (Mateos et al. (2010);Palumbo et al. (2006)). Decreasing the morbidity associated with high dose steroid use by using better-tolerated regimens addresses a large unmet need of the myeloma patient population.

Study groups in NCT06212596
Study groupRoleWhat they receive
Selinexor cylophosphamide prednisoneExperimentalParticipants will receive treatment with Selinexor, Cyclophosphamide and Prednisone.
Receives: Drug: Selinexor; Drug: Cyclophosphamide; Drug: Prednisone
Cyclophosphamide predinisoneActive comparatorParticipants will receive treatment with Cyclophosphamide and Prednisone. Participants who experience disease progression on the CP arm, may receive SCP.
Receives: Drug: Cyclophosphamide; Drug: Prednisone

What is being measured

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

  1. Progression free survival at 6 months

    To determine whether the addition of selinexor to cyclophosphamide and prednisone may lead to an increased progression free survival

    Measured: 6 months

Secondary outcomes (7)

  1. Number of SAEs, SARs, SUSARs

    Safety will be reported based on the number of safety events seen

    Measured: 3 1/2 years

  2. Progression free survival

    Progression-free survival is defined as the time from randomisation to first documented evidence of disease progression or death. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression-free.

    Measured: 6 and 12 months

  3. Maximum response

    Response to treatment is assessed as per the Modified IWG Uniform Response Criteria given in Appendix 1. Maximum response is defined as the proportion of participants achieving each of the response categories sCR, CR, VGPR, PR, MR or SD as their maximum response to treatment. Participants who do not have at least one post-baseline response assessment will be excluded from the analysis of this endpoint.

    Measured: 6 and 12 months

  4. Time to maximum response

    Time to maximum response is defined as the time from randomisation until the participant achieves any of the categories sCR, CR, VGPR, PR, MR or SD as their maximum response. Participants who do not achieve a maximum response will either be classed as having had a competing risk or censored at the time of disease progression or death, whichever is earlier

    Measured: 6 and 12 months

  5. Duration of response

    Response duration is defined as the time from the first observation of at least PR until disease progression. Participants who die due to causes other than progression will be censored at the time of death. Participants who, at the time of analysis, have not progressed, will be censored at the date last known to be alive and progression-free. Participants not achieving at least a PR are not included in this analysis.

    Measured: 6 and 12 months

  6. Compliance to therapy

    Compliance to therapy will be summarised by mean dose, number of doses missed and number of dose reductions and delays throughout the treatment period. The reasons for missed and dose modifications will also be summarised.

    Measured: 6 months

  7. Number of participants with treatment-related adverse events as assessed by CTCAE 4.0 (time frame: 3 ½ years)

    Toxicity analyses will summarise by trial arm and show the proportion of participants experiencing each grade of toxicity overall, and during each treatment cycle. For more detailed summaries, this information will also be broken down into the different types of toxicity.

    Measured: 3 1/2 years

Timeline

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

  1. First posted19 Jan 2024
  2. Study start16 Jul 2018
  3. Primary completion25 Oct 2022
  4. Study completion14 Nov 2023

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
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisone (SCP) or cyclophosphamide + prednisone (CP). A computer-generated minimisation programme that incorporates a random element will be used to ensure treatment groups are well-balanced for pre-specified factors: * Age (\<60 vs. 60-69 years vs. ≥70 years ) * Number of prior lines of therapy (≤3 vs. \>3) A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 participants in the CP arm). Participants who experience disease progression on the CP arm, may receive SCP, once progression has been confirmed by the CTRU and the participant has been deemed eligible to receive SCP. Patients randomised to SCP have no further trial treatment stipulated following SCP therapy. The analysis of the treatment switch phase of the trial is exploratory.
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06212596
Sponsor's protocol ID
HM17/95228
Other IDs
2017-001736-19, 2017
Acronym
MUKtwelve
Status last verified
Jan 2024
First submitted
14 Jun 2017
Last updated
19 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selinexor, Cyclophosphamide and Prednisone in people with Relapsed or Refractory Multiple Myeloma, run by University of Leeds at 13 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 20 inclusion and 43 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: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 at 6 months (time frame: 6 months). 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 NCT06212596.

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 19 Jan 2024.

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