Multiple MyelomaPhase 1NCT02616640
A Study to Determine Dose and Regimen of Durvalumab as Monotherapy or in Combination With Pomalidomide With or Without Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
A Phase 1 study testing Durvalumab, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 22 sites in 7 countries.
Trial summary
This is a multicenter, open-label, Phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM with or without low dose dex in subjects with RRMM. 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?
- Durvalumab, Pomalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 22 sitesin 7 countries
- Study dates
- 11 Jan 2016to 30 Jul 2024
- Phase
- Phase 1
- 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
- Has a confirmed diagnosis of active multiple myeloma and measurable disease.
- Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy
- Must have failed last line of treatment (refractory to last line of treatment).
- Must have achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing Progressive disease (PD) (relapsed)
- Prior anti-myeloma treatments must have included a lenalidomide AND proteasome inhibitor alone or in combination.
- Has performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- The extramedullary plasmacytoma (EMP) sub-group, must have radiologically measurable EMP disease (soft tissue or bone related) that is amenable to biopsy and does not need to have measurable disease.
Who cannot join
- Has non-secretory or oligosecretory multiple myeloma
- Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1
- Has undergone prior organ or allogeneic hematopoetic stem cell transplantation
- Has received previous therapy with pomalidomide and did not achieve at least a stable disease
- Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), antiprogrammed death-ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
- Has received prior treatment with a monoclonal antibody within 5 half-lives of Study Day 1
Show all 18Show fewer
- Has received investigational agents within 28 days or 5 half-lives (whichever is longer) of Study Day 1
- Has received live, attenuated vaccine within 30 days prior to Study Day 1
- Had rash ≥ Grade 3 during prior thalidomide, lenalidomide, or pomalidomide therapy
- Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, POM, or dex
- Has peripheral neuropathy ≥ Grade 2
- Has a known additional malignancy that is progressing or requires active treatment (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
- Is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C
- Has a prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years (with the exception Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer [T1a or T1b] or prostate cancer that is curative)
- Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma
- Has clinically significant cardiac disease
- Is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during the participation in the study
- Is a current smoker
Trial locations and contacts
22 sites in 7 countries.
22 sites in 7 countries
United States8 sites
Local Institution - 102
Baltimore, Maryland, 21231
Local Institution - 114
Boston, Massachusetts, 02114
Local Institution - 108
Boston, Massachusetts, 02115
Local Institution - 115
Boston, Massachusetts, 02215
Local Institution - 106
Charlotte, North Carolina, 28204
Local Institution - 110
Cleveland, Ohio, 44195
Local Institution - 107
Milwaukee, Wisconsin, 53226
Local Institution - 105
New York, New York, 10065
Spain4 sites
Local Institution - 501
Barcelona, 08916
Local Institution - 504
Madrid, 28041
Local Institution - 502
Pamplona, 31008
Local Institution - 505
Valencia, 46026
France3 sites
Local Institution - 601
Lille, 59037
Local Institution - 602
Poitiers, 86021
Local Institution - 603
Toulouse, 31059
Italy3 sites
Local Institution - 403
Pavia, 27100
Local Institution - 405
Rozzano (MI), 20089
Local Institution - 401
Torino, 10126
Netherlands2 sites
Local Institution - 702
Amsterdam, 1081 HV
Local Institution - 701
Rotterdam, 3015 CN
About this study
Official title: A Phase IB Multicenter, Open-label Study To Determine The Recommended Dose And Regimen Of Durvalumab (MEDI4736) Either As Monotherapy or In Combination With Pomalidomide (POM) With Or Without Low-Dose Dexamethasone (DEX) In Subjects With Relapsed And Refractory Multiple Myeloma (RRMM)
This is a multicenter, open-label, Phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM with or without low dose dex in subjects with RRMM. The study will consist of a dose-finding portion as well as a parallel dose-expansion portion to determine the optimal dose and regimen.
On 05 Sep 2017, a Partial Clinical Hold was placed on this study by the United States (US) Food and Drug Administration (FDA). The decision by the FDA was based on data related to risks of anti-programmed cell death-1 (PD-1) antibody, pembrolizumab, in combination with IMiDs® immunomodulatory drugs in patients with multiple myeloma. As a result, enrollment into this study has been discontinued. Subjects who are receiving clinical benefit, based on the discretion of the investigator, may remain on study treatment after being reconsented.
- Conditions
- Multiple Myeloma
- Being tested
- Durvalumab, Pomalidomide, Dexamethasone
- Keywords
- Multiple Myeloma, Relapsed, Refractory, MEDI4736, Durvalumab, Pomalidomide (POM), Dexamethasone (DEX), PD-L1
- 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.
DurvalumabDrug
Also called MEDI4736
PomalidomideDrug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab monotherapy | Experimental | Intravenous (IV) durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle Receives: Drug: Durvalumab |
| Durvalumab + pomalidomide (POM) | Experimental | IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle and Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle Receives: Drug: Durvalumab; Drug: Pomalidomide |
| Durvalumab + pomalidomide (POM) + dexamethasone (dex) | Experimental | IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle with Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle and Oral dex 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle Receives: Drug: Durvalumab; Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicities (DLTs)
Number of participants with DLTs in the first cycle of treatment
Measured: Approximately 1 month
Secondary outcomes (10)
Adverse Events (AEs)
Number of participants with adverse events
Measured: Up to approximately 2 year
Overall response rate (ORR)
Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria
Measured: Up to approximately 2 year
Time to response (TTR)
Time from first dose to the first documentation of response (Partial Response [PR] or greater)
Measured: Up to approximately 2 year
Duration of response (DOR)
Is defined as time from the earliest date of documented response (partial response (PR) or better) to the earliest date when disease progression was confirmed
Measured: Up to approximately 2 year
Pharmacokinetics- Cmax
Maximum observed concentration
Measured: Up to approximately 1 year
Pharmacokinetics- AUC
Area under the concentration-time curve
Measured: Up to approximately 1 year
Pharmacokinetics- Tmax
Time to maximum concentration
Measured: Up to approximately 1 year
Pharmacokinetics- t1/2
Terminal elimination half-life
Measured: Up to approximately 1 year
Pharmacokinetics- CL/F
Apparent total body clearance
Measured: Up to approximately 1 year
Pharmacokinetics- Vz/F
Volume of distribution
Measured: Up to approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2015 (estimated)
- Study start11 Jan 2016
- Primary completion23 Nov 2018
- Study completion30 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lars Sternas, MD, PhD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02616640
- Sponsor's protocol ID
- MEDI4736-MM-001
- Status last verified
- Aug 2024
- First submitted
- 25 Nov 2015
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Young MH, Pietz G, Whalen E, Copeland W, Thompson E, Fox BA, Newhall KJ. Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma. Sci Rep. 2021 Aug 12;11(1):16460. doi: 10.1038/s41598-021-95902-x.
PubMed 34385543
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB Multicenter, Open-label Study To Determine The Recommended Dose And Regimen Of Durvalumab (MEDI4736) Either As Monotherapy or In Combination With Pomalidomide (POM) With Or Without Low-Dose Dexamethasone (DEX) In Subjects With Relapsed And Refractory Multiple Myeloma (RRMM)
- ClinicalTrials.gov ID
- NCT02616640
- Acronym / sponsor ID
- MEDI4736-MM-001
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Relapsed, Refractory, MEDI4736, Durvalumab, Pomalidomide (POM), Dexamethasone (DEX), PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2016 (actual)
- Primary completion
- 23 Nov 2018 (actual)
- Study completion
- 30 Jul 2024 (actual)
- First posted
- 30 Nov 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 is a multicenter, open-label, Phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM with or without low dose dex in subjects with RRMM. The study will consist of a dose-finding portion as well as a parallel dose-expansion portion to determine the optimal dose and regimen.
On 05 Sep 2017, a Partial Clinical Hold was placed on this study by the United States (US) Food and Drug Administration (FDA). The decision by the FDA was based on data related to risks of anti-programmed cell death-1 (PD-1) antibody, pembrolizumab, in combination with IMiDs® immunomodulatory drugs in patients with multiple myeloma. As a result, enrollment into this study has been discontinued. Subjects who are receiving clinical benefit, based on the discretion of the investigator, may remain on study treatment after being reconsented.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Durvalumab monotherapy | Experimental | Drug: DurvalumabIntravenous (IV) durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle |
| Durvalumab + pomalidomide (POM) | Experimental | Drug: Durvalumab, Drug: PomalidomideIV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle and Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle |
| Durvalumab + pomalidomide (POM) + dexamethasone (dex) | Experimental | Drug: Durvalumab, Drug: Pomalidomide, Drug: DexamethasoneIV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle with Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle and Oral dex 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Has a confirmed diagnosis of active multiple myeloma and measurable disease.
- Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy
- Must have failed last line of treatment (refractory to last line of treatment).
- Must have achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing Progressive disease (PD) (relapsed)
- Prior anti-myeloma treatments must have included a lenalidomide AND proteasome inhibitor alone or in combination.
Key exclusion criteria (18 listed)
- Has non-secretory or oligosecretory multiple myeloma
- Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1
- Has undergone prior organ or allogeneic hematopoetic stem cell transplantation
- Has received previous therapy with pomalidomide and did not achieve at least a stable disease
- Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), antiprogrammed death-ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
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 |
|---|---|---|
| DurvalumabAlso: MEDI4736 | Drug | Durvalumab + pomalidomide (POM), Durvalumab + pomalidomide (POM) + dexamethasone (dex), Durvalumab monotherapy |
| Pomalidomide | Drug | Durvalumab + pomalidomide (POM), Durvalumab + pomalidomide (POM) + dexamethasone (dex) |
| Dexamethasone | Drug | Durvalumab + pomalidomide (POM) + dexamethasone (dex) |
Primary outcome
Dose-limiting Toxicities (DLTs)
Time frame: Approximately 1 month
Number of participants with DLTs in the first cycle of treatment
10 secondary outcomes
Adverse Events (AEs)
Time frame: Up to approximately 2 year
Overall response rate (ORR)
Time frame: Up to approximately 2 year
Time to response (TTR)
Time frame: Up to approximately 2 year
Duration of response (DOR)
Time frame: Up to approximately 2 year
Pharmacokinetics- Cmax
Time frame: Up to approximately 1 year
Pharmacokinetics- AUC
Time frame: Up to approximately 1 year
Pharmacokinetics- Tmax
Time frame: Up to approximately 1 year
Pharmacokinetics- t1/2
Time frame: Up to approximately 1 year
Pharmacokinetics- CL/F
Time frame: Up to approximately 1 year
Pharmacokinetics- Vz/F
Time frame: Up to approximately 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 34385543Young MH, Pietz G, Whalen E, Copeland W, Thompson E, Fox BA, Newhall KJ. Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma. Sci Rep. 2021 Aug 12;11(1):16460. doi: 10.1038/s41598-021-95902-x.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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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.
Lars Sternas, MD, PhD study director
Celgene Corporation
22 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Durvalumab, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 22 sites in 7 countries.
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 7 inclusion and 18 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 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Spain, France, Italy, Netherlands and 2 more countries. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Dose-limiting Toxicities (DLTs) (time frame: Approximately 1 month). 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 NCT02616640, which also lists 1 linked publication.
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 Sep 2024.