Multiple MyelomaPhase 1/2NCT02289222
1454GCC: Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma
A Phase 1/2 study testing MK-3475, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Ashraf Badros at 1 site in United States.
Trial summary
This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14. 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?
- MK-3475, 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
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2014to 7 Aug 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Confirmed diagnosis of relapsed and/or refractory MM according to International Myeloma Working Group guidelines (2003)
- Received two lines of prior therapy that includes an IMiD (lenalidomide or thalidomide) and a proteasome inhibitor (bortezomib and/or carfilzomib) (used either separately or in combination). (a). Prior pomalidomide therapy is permitted, provided the patient achieved at least a partial remission and had not progressed for 3 months after stopping therapy.
- Measureable disease as defined by the protocol (assessed within 28 days prior to registration).
- Be willing and able to provide written informed consent/assent for the trial.
- Be over 18 years of age on day of signing informed consent.
- Have a performance status of 2 on the ECOG Performance Scale.
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- Demonstrate adequate organ function as defined by the protocol.
- Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study drug.
- Male subjects should agree to use an adequate method of contraception.
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency (HIV) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.)
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or situ cervical cancer that has undergone potentially curative therapy.
- Has known active central nervous system disease and/or carcinomatous meningitis.
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- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Pregnant or breastfeeding, or expecting to conceive or father children during study participation.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as per the protocol.
- has known active Hepatitis B or Hepatitis C.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201-1592
About this study
Official title: 1454GCC: Phase I/II Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma
This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14.
Read the detailed description
This phase I/II study is focused on patients with relapsed or refractory multiple myeloma. MK-3475 will be given as an intravenous infusion at every 2 weeks. Treatment will be administered on an outpatient basis.
- Conditions
- Multiple Myeloma
- Being tested
- MK-3475, Pomalidomide, Dexamethasone
- Keywords
- Relapsed/Refractory, MK-3475 & Pomalidomide, Immunotherapy
- 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.
MK-3475Drug
Also called Generic name: Pembrolizumab - Trade name: Keytruda
Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks.
PomalidomideDrug
Also called Pomalyst, CC-4047, Actimid
Pomalidomide is given at standard dose of 4 mg daily orally for 21 days
DexamethasoneDrug
Also called Decadron
Dexamethasone is given at 40 mg orally weekly
| Study group | Role | What they receive |
|---|---|---|
| Pomalidomide, Dexamethasone & MK-3475 | Experimental | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). Receives: Drug: MK-3475; Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With Adverse Events
Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475
Measured: 24 month
Secondary outcomes (2)
PD-LI Expression On Myeloma Cells
The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses ≥ very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses.
Measured: Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months)
Time to Progression Free Survival (PFS)
PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile.
Measured: PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2014 (estimated)
- Study start30 Dec 2014
- Primary completion7 Aug 2017
- Study completion7 Aug 2017
Why it stopped: Due to the inclusion of an IMid in combination with pembrolizumab, Study Sponsor terminated the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ashraf Badros
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Ashraf Badros, University of Maryland, Baltimore
- Investigators
- Ashraf Z Badros, M.B.,Ch.B, Principal investigator, University of Maryland Greenebaum Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02289222
- Sponsor's protocol ID
- HP-00061522; GCC1454
- Status last verified
- Nov 2019
- First submitted
- 17 Oct 2014
- Last updated
- 5 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Badros A, Hyjek E, Ma N, Lesokhin A, Dogan A, Rapoport AP, Kocoglu M, Lederer E, Philip S, Milliron T, Dell C, Goloubeva O, Singh Z. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1189-1197. doi: 10.1182/blood-2017-03-775122. Epub 2017 May 1.
PubMed 28461396
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1454GCC: Phase I/II Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02289222
- Acronym / sponsor ID
- HP-00061522; GCC1454
- Conditions
- Multiple Myeloma
- Keywords
- Relapsed/Refractory, MK-3475 & Pomalidomide, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the inclusion of an IMid in combination with pembrolizumab, Study Sponsor terminated the study.
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Ashraf BadrosUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 30 Dec 2014 (actual)
- Primary completion
- 7 Aug 2017 (actual)
- Study completion
- 7 Aug 2017 (actual)
- First posted
- 13 Nov 2014 (estimated)
- Results
- Posted 1 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14.
Detailed description
This phase I/II study is focused on patients with relapsed or refractory multiple myeloma. MK-3475 will be given as an intravenous infusion at every 2 weeks. Treatment will be administered on an outpatient basis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide, Dexamethasone & MK-3475 | Experimental | Drug: MK-3475, Drug: Pomalidomide, Drug: DexamethasonePomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Confirmed diagnosis of relapsed and/or refractory MM according to International Myeloma Working Group guidelines (2003)
- Received two lines of prior therapy that includes an IMiD (lenalidomide or thalidomide) and a proteasome inhibitor (bortezomib and/or carfilzomib) (used either separately or in combination). (a). Prior pomalidomide therapy is permitted, provided the patient achieved at least a partial remission and had not progressed for 3 months after stopping therapy.
- Measureable disease as defined by the protocol (assessed within 28 days prior to registration).
- Be willing and able to provide written informed consent/assent for the trial.
- Be over 18 years of age on day of signing informed consent.
Key exclusion criteria (16 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency (HIV) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.)
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or situ cervical cancer that has undergone potentially curative therapy.
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 |
|---|---|---|
| MK-3475Also: Generic name: Pembrolizumab - Trade name: KeytrudaAnti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks. | Drug | Pomalidomide, Dexamethasone & MK-3475 |
| PomalidomideAlso: Pomalyst, CC-4047, ActimidPomalidomide is given at standard dose of 4 mg daily orally for 21 days | Drug | Pomalidomide, Dexamethasone & MK-3475 |
| DexamethasoneAlso: DecadronDexamethasone is given at 40 mg orally weekly | Drug | Pomalidomide, Dexamethasone & MK-3475 |
Primary outcome
The Number of Participants With Adverse Events
Time frame: 24 month
Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475
2 secondary outcomes
PD-LI Expression On Myeloma Cells
Time frame: Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months)
Time to Progression Free Survival (PFS)
Time frame: PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28461396Badros A, Hyjek E, Ma N, Lesokhin A, Dogan A, Rapoport AP, Kocoglu M, Lederer E, Philip S, Milliron T, Dell C, Goloubeva O, Singh Z. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1189-1197. doi: 10.1182/blood-2017-03-775122. Epub 2017 May 1.
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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.
Ashraf Z Badros, M.B.,Ch.B principal investigator
University of Maryland Greenebaum Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MK-3475, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Ashraf Badros at 1 site in United States.
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 9 inclusion and 16 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: stopped early, as of the sponsor's last update on 5 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 1 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Participants With Adverse Events (time frame: 24 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 NCT02289222, 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 5 Nov 2019.