Multiple MyelomaPhase 2MUKsevenNCT02406222
Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)
A Phase 2 study testing Pomalidomide, Dexamethasone and Cyclophosphamide in people with Multiple Myeloma, run by University of Leeds at 21 sites in United Kingdom.
Trial summary
This study is determining whether the addition of cyclophosphamide to pomalidomide and dexamethasone improves progression free survival in patients with relapsed refractory myeloma (RRMM) compare to pomalidomide and dexamethasone alone. Patients will be randomised on a 1:1 basis to receive CPD or Pd. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Pomalidomide, Dexamethasone and Cyclophosphamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 21 sitesUnited Kingdom
- Study dates
- Mar 2016to Jun 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Diagnosed with symptomatic multiple myeloma (according to International Myeloma Working Group (IMWG) 2009 criteria) and have measurable disease
- Participants must require therapy for relapsed and/or refractory disease
- Participants must have received ≥ 2 treatment lines of anti-myeloma therapy (induction therapy followed by autologous stem-cell transplantation (ASCT) and consolidation/maintenance will be considered as one line).
- Participants must have received prior treatment with both lenalidomide and proteasome inhibitor, either as single agents or in combination regimens
- All participants must have failed treatment with either lenalidomide and proteasome inhibitor in one of the following ways:
- Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or proteasome inhibitor ; or
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- In case of prior response [≥ partial response (PR)] to lenalidomide or proteasome inhibitor, participants must have relapsed within 6 months after stopping treatment with lenalidomide and/or proteasome inhibitor containing regimens; or
- Participants who have not had a ≥ minimal response (MR) despite receiving at least 4 cycles of treatment or who have developed intolerance/toxicity after a minimum of two cycles of lenalidomide and/or proteasome inhibitor containing regimen
- Patients must have received adequate prior alkylator therapy in one of the following ways
- As part of a stem cell transplant; or
- A minimum of 4 consecutive cycles of an alkylator based therapy; or
- Progression on treatment with an alkylator; provided that the participant received at least 2 cycles of an alkylator containing therapy.
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Required laboratory values within 14 days of treatment:
- Absolute neutrophil count ≥ 1.0 x109 /L (growth factor support is permitted)
- Platelet count ≥ 30 x 109/L (platelet transfusion is permitted)
- Creatinine clearance > 30 mL/min
- Corrected serum calcium ≤ 3.5 mmol/L
- Haemoglobin ≥ 8 g/dL (blood transfusion support is permitted)
- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) < 3 times Upper Limit of Normal (ULN)
- Serum total bilirubin < 17 µmol/l
- Participants must consent to provide the bone marrow samples specified at screening and throughout the trial, in order to enter the trial. Confirmation of receipt of the sample from the lab must be received before treatment commences..
- Able to give informed consent and willing to follow trial protocol
- Aged over 18 or over
- Females of childbearing potential (FCBP) must agree to utilise one reliable form of contraception for 28 days prior to starting trial treatment, during the trial, and for 28 days after trial treatment discontinuation and even in the case of dose interruption and must agree to regular pregnancy testing during this timeframe
- Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation
- Males must agree to use a latex condom during any sexual contact with FCBP during the trial, including during any dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy
- Males must also agree to refrain from donating semen or sperm while on pomalidomide, including during any dose interruptions and for 28 days after discontinuation from this trial
- All participants must agree to refrain from donation blood while on trial drug, including during dose interruptions and for 28 days after discontinuation from this trial
Who cannot join
- Previous therapy with pomalidomide
- Hypersensitivity to thalidomide, lenalidomide, cyclophosphamide or dexamethasone
- Participants with non-secretory multiple myeloma
- Peripheral neuropathy ≥ Grade 3
- Participants who have received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
- Participants who are planned for a stem cell transplant post MUK Seven trial treatment
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- Antitumour therapies including investigational medicinal products at any dose within 28 days before the start of protocol treatment (or 5 half-lives, whichever is longer). Bisphosphonates for bone disease and radiotherapy for palliative intent are permitted.
- Participants with any of the following
- Uncontrolled congestive heart failure
- Myocardial infarction within 12 months prior to starting trial treatment
- Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
- Participants with gastrointestinal disease that may significantly alter absorption of pomalidomide
- Participants with a history of other malignancies within 5 years before the date of study entry (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that is considered cured with minimal risk of recurrence within 5 years).
- Participants unable or unwilling to undergo antithrombotic prophylactic treatment
- Pregnant or breastfeeding females
- Participants known to be seropositive for HIV, or active infectious hepatitis A, B or C
- Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the trial
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United Kingdom21 sites
Belfast Health & Social Care Trust
Belfast, BT9 7AB
University of Birmingham NHS Foundation Trust
Birmingham, B15 2TH
Birmingham Heartlands Hospital
Birmingham, B9 5SS
Royal Sussex County Hospital
Brighton, BN2 5BE
Queens Hospital
Burton-on-Trent, DE13 0RB
University Hospital of Wales NHS Trust
Cardiff, CF14 4XW
Ninewells Hospital
Dundee, DD1 9SY
Beatson Oncology Centre
Glasgow
St James's Hopsital
Leeds, LS9 7TF
University Hospital of Leicester NHS Trust
Leicester, LE1 5WW
St Bartholomew Hospital
London, EC1M 6BQ
University College London Hospital
London, NW1 2BU
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Imperial College Hospital
London, W2 1NY
Central Manchester Univeristy Hospital NHS Trust
Manchester, M13 9WL
The Christie Hospital
Manchester, M20 4BX
Churchill Hospital
Oxford, OX3 7LE
Sheffield Teaching Hospitals NHS FoundationTrust
Sheffield, S10 2RB
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE
New Cross Hospital
Wolverhampton, WV10 0QP
About this study
This study is determining whether the addition of cyclophosphamide to pomalidomide and dexamethasone improves progression free survival in patients with relapsed refractory myeloma (RRMM) compare to pomalidomide and dexamethasone alone. Patients will be randomised on a 1:1 basis to receive CPD or Pd. Treatment will be continued until disease progression or unacceptable toxicity.
Read the detailed description
Multiple myeloma is the second most common hematologic malignancy in the European Union (EU), responsible for an estimated 21,000 deaths in the EU in 2008. For patients that relapse or are refractory to current standard treatment (combination of bortezomib/lenalidomide, dexamethasone and an alkylating agent) there are few options available and therefore the prognosis within this group is often poor with response to treatment decreasing with successive relapses until resistant disease develops. . Current standard treatment at first relapse in the UK is the use of bortezomib in combination with dexamethasone and cyclophosphamide. Another common treatment is lenalidomide given with dexamethasone and cyclophosphamide. The addition of cyclophosphamide has demonstrated to improve treatment outcomes whilst being tolerated well. A recent clinical study has shown the addition of cyclophosphamide to the combination of pomalidomide and dexamethasone has shown to be safe and tolerable and beneficial in terms of treatment outcomes. The primary aim of this study is to investigate whether the addition of cyclophosphamide to pomalidomide and dexamethasone leads to an improved progression free survival. A secondary aim is to identify markers from clinical material that will predict response to pomalidomide in a group of relapsed and refractory multiple myeloma (RRMM) patients to provide important information for use in discussions with NICE on how best to improve the value and use of pomalidomide in the UK in the RRMM setting.
- Conditions
- Multiple Myeloma
- Being tested
- Pomalidomide, Dexamethasone, Cyclophosphamide
- Keywords
- Relapsed, Refractory, Pomalidomide, Dexamethasone, Cyclophosphamide
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PomalidomideDrug
Chemotherapy
DexamethasoneDrug
Chemotherapy
CyclophosphamideDrug
Chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Pomalidomide and Dexamethasone | Active comparator | Pomalidomide and Dexamethasone will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal.
Dosing schedule:
* Pomalidomide 4mg orally on days 1-21
* Dexamethasone 40mg orally on days 1, 8, 15 and 22 Receives: Drug: Pomalidomide; Drug: Dexamethasone |
| Pomalidomide Dexamethasone Cyclophosphamide | Experimental | Pomalidomide, Dexamethasone and Cyclophosphamide will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal.
Dosing schedule:
* Pomalidomide 4mg orally on days 1-21
* Dexamethasone 40mg orally on days 1, 8, 15 and 22
* Cyclophosphamide 500mg orally on days 1, 8 and 15 Receives: Drug: Pomalidomide; Drug: Dexamethasone; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
To determine whether the addition of cyclophosphamide to pomalidomide and dexamethasone (CPD) improves progression-free survival in patients with relapsed refractory myeloma (RRMM) in the UK, compared to pomalidomide and dexamethasone (Pd) alone
Measured: From randomisation up to 72 months
Secondary outcomes (8)
Maximum response overall
To determine the maximum response achieved from treatment
Measured: From the start of treatment up to 72 months
Response to treatment
Determine the response to treatment
Measured: From the start of treatment up to 72 months
Clinical benefit rate overall
Determine any clinical benefit that is derived from treatment
Measured: From the start of treatment up to 72 months
Time to maximum response
Determine the time to maximum response to treatment
Measured: From the start of treatment up to 72 months
Duration of response
Determine the duration that the response to treatment lasts for
Measured: From the start of treatment up to 72 months
Overall survival
Determine overall survival for all patients that receive treatment
Measured: Date of randomisation to death, up to 72 months
Treatment compliance
Measured by treatment delays and missed treatment doses
Measured: From the start of treatment up to end of treatment
Safety and Toxicity
Measured by adverse reactions and serious adverse event reporting
Measured: Time of registration to 28 days post treatment discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2015 (estimated)
- Study startMar 2016
- Primary completionDec 2022
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- Myeloma UK, Celgene
- Responsible party
- Sponsor
- Investigators
- Martin Kaiser, Dr, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02406222
- Sponsor's protocol ID
- HM13/10758
- Acronym
- MUKseven
- Status last verified
- Dec 2024
- First submitted
- 18 Feb 2015
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)
- ClinicalTrials.gov ID
- NCT02406222
- Acronym / sponsor ID
- MUKseven / HM13/10758
- Conditions
- Multiple Myeloma
- Keywords
- Relapsed, Refractory, Pomalidomide, Dexamethasone, Cyclophosphamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 124 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- Myeloma UK, Celgene
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2022 (actual)
- Study completion
- Jun 2025 (estimated)
- First posted
- 2 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is determining whether the addition of cyclophosphamide to pomalidomide and dexamethasone improves progression free survival in patients with relapsed refractory myeloma (RRMM) compare to pomalidomide and dexamethasone alone. Patients will be randomised on a 1:1 basis to receive CPD or Pd. Treatment will be continued until disease progression or unacceptable toxicity.
Detailed description
Multiple myeloma is the second most common hematologic malignancy in the European Union (EU), responsible for an estimated 21,000 deaths in the EU in 2008. For patients that relapse or are refractory to current standard treatment (combination of bortezomib/lenalidomide, dexamethasone and an alkylating agent) there are few options available and therefore the prognosis within this group is often poor with response to treatment decreasing with successive relapses until resistant disease develops. . Current standard treatment at first relapse in the UK is the use of bortezomib in combination with dexamethasone and cyclophosphamide. Another common treatment is lenalidomide given with dexamethasone and cyclophosphamide. The addition of cyclophosphamide has demonstrated to improve treatment outcomes whilst being tolerated well. A recent clinical study has shown the addition of cyclophosphamide to the combination of pomalidomide and dexamethasone has shown to be safe and tolerable and beneficial in terms of treatment outcomes. The primary aim of this study is to investigate whether the addition of cyclophosphamide to pomalidomide and dexamethasone leads to an improved progression free survival. A secondary aim is to identify markers from clinical material that will predict response to pomalidomide in a group of relapsed and refractory multiple myeloma (RRMM) patients to provide important information for use in discussions with NICE on how best to improve the value and use of pomalidomide in the UK in the RRMM setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide and Dexamethasone | Active comparator | Drug: Pomalidomide, Drug: DexamethasonePomalidomide and Dexamethasone will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Pomalidomide 4mg orally on days 1-21 * Dexamethasone 40mg orally on days 1, 8, 15 and 22 |
| Pomalidomide Dexamethasone Cyclophosphamide | Experimental | Drug: Pomalidomide, Drug: Dexamethasone, Drug: CyclophosphamidePomalidomide, Dexamethasone and Cyclophosphamide will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Pomalidomide 4mg orally on days 1-21 * Dexamethasone 40mg orally on days 1, 8, 15 and 22 * Cyclophosphamide 500mg orally on days 1, 8 and 15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Diagnosed with symptomatic multiple myeloma (according to International Myeloma Working Group (IMWG) 2009 criteria) and have measurable disease
- Participants must require therapy for relapsed and/or refractory disease
- Participants must have received ≥ 2 treatment lines of anti-myeloma therapy (induction therapy followed by autologous stem-cell transplantation (ASCT) and consolidation/maintenance will be considered as one line).
- Participants must have received prior treatment with both lenalidomide and proteasome inhibitor, either as single agents or in combination regimens
- All participants must have failed treatment with either lenalidomide and proteasome inhibitor in one of the following ways:
Key exclusion criteria (17 listed)
- Previous therapy with pomalidomide
- Hypersensitivity to thalidomide, lenalidomide, cyclophosphamide or dexamethasone
- Participants with non-secretory multiple myeloma
- Peripheral neuropathy ≥ Grade 3
- Participants who have received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PomalidomideChemotherapy | Drug | Pomalidomide Dexamethasone Cyclophosphamide, Pomalidomide and Dexamethasone |
| DexamethasoneChemotherapy | Drug | Pomalidomide Dexamethasone Cyclophosphamide, Pomalidomide and Dexamethasone |
| CyclophosphamideChemotherapy | Drug | Pomalidomide Dexamethasone Cyclophosphamide |
Primary outcome
Progression free survival
Time frame: From randomisation up to 72 months
To determine whether the addition of cyclophosphamide to pomalidomide and dexamethasone (CPD) improves progression-free survival in patients with relapsed refractory myeloma (RRMM) in the UK, compared to pomalidomide and dexamethasone (Pd) alone
8 secondary outcomes
Maximum response overall
Time frame: From the start of treatment up to 72 months
Response to treatment
Time frame: From the start of treatment up to 72 months
Clinical benefit rate overall
Time frame: From the start of treatment up to 72 months
Time to maximum response
Time frame: From the start of treatment up to 72 months
Duration of response
Time frame: From the start of treatment up to 72 months
Overall survival
Time frame: Date of randomisation to death, up to 72 months
Treatment compliance
Time frame: From the start of treatment up to end of treatment
Safety and Toxicity
Time frame: Time of registration to 28 days post treatment discontinuation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Kaiser, Dr principal investigator
Royal Marsden NHS Foundation Trust
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pomalidomide, Dexamethasone and Cyclophosphamide 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 30 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 5 Dec 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?
This study is still under way. Results are not available in the source record yet.
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: From randomisation up to 72 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2024.