Smoldering Multiple MyelomaPhase 2NCT03850522
PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma
A Phase 2 study testing PD-L1 peptide in people with Smoldering Multiple Myeloma, run by Lene Meldgaard Knudsen at 1 site in Denmark.
Trial summary
This study is evaluating a new vaccine against PD-L1 as a possible treatment for high-risk smoldering multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoldering Multiple Myeloma
- What is being tested?
- PD-L1 peptide
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteDenmark
- Study dates
- 18 Feb 2019to 10 Mar 2021
- 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
- Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003)
- Serum M-component >30g/L and/or
- Urine M-component ≥ 500mg/24 hours and/or
- ≥10% clonal plasma cells in bone marrow
- and no CRAB criteria or myeloma defining events (see exclusion criteria)
- High risk of progression to symptomatic multiple myeloma defined by the presence of ≥ 2 of the risk factors below:
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- Bone marrow Plasma Cells (BMPCs) ≥ 20%
- M-component > 2g/dL
- FLC ratio > 20
- Age ≥18 years
- Performance status ≤ 2 (ECOG-scale)
- Expected survival > 3 months
- Sufficient liver function, i.e.
- ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l
- Bilirubin < 30 U/l
- Women agreement to use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 120 days after the last treatment.
- For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.
- The accepted contraceptive methods are
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation. Oral, intravaginal or transdermal.
- Progestogen-only hormonal contraception associated with inhibition of ovulation. Oral, injectable, implantable.
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence
Who cannot join
- Non-secretory myeloma
- Patients fulfilling CRAB criteria:
- C: Hypercalcemia,
- 1. s-Ca-ion >1,40 mmol/L, attributable to myeloma ii. R: Renal failure
- Estimated or measured creatinine clearance <40ml/min, attributable to myeloma
- Increased s-creatinine, attributable to myeloma
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- Decrease in estimated or measured creatinine clearance <35% within a year, attributable to myeloma
- Renal biopsy-verified renal changes attributable to myeloma iii. A: Anemia, Hgb < 6,3mmol/L (10g/dl), attributable to myeloma iv. B: Bone lesions on X-ray, CT or PET-CT
- Evidence of myeloma defining events i. Clonal bone marrow plasma cell percentage ≥ 60% ii. Ratio of involved/uninvolved serum free light chain ratio ≥ 100 iii. >1 focal lesions on MRI studies, if clinically indicated
- Plasma cell leukemia
- Signs of amyloidosis
- Other malignancies in the medical history excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer and patients cured for another malignant disease with no sign of relapse two years after ended treatment.
- Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
- Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis
- Serious known allergies or earlier anaphylactic reactions.
- Known sensibility towards Montanide ISA-51
- Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
- Pregnant and breastfeeding women.
- Fertile women not using secure contraception with a failure rate less than < 1%
- Patients taking immune suppressive medications incl. corticosteroids and methotrexate at the time of enrollment
- Psychiatric disorders that per investigator judgment could influence compliance.
- Treatment with other experimental drugs
- Concurrent treatment with other anti-cancer drugs.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Hematology, Universityhospital Herlev and Gentofte
Herlev, 2730
About this study
Official title: Phase IIa Trial of PD-L1 Peptide Vaccination as Monotherapy in High Risk Smoldering Multiple Myeloma
This study is evaluating a new vaccine against PD-L1 as a possible treatment for high-risk smoldering multiple myeloma.
Read the detailed description
Smoldering multiple myeloma is an asymptomatic disorder with an annual risk of 10% of progression to the incurable cancer multiple myeloma. While many patients live for many years without progression, high risk patients have a median risk of progression of 29 months. No therapy has been approved for this indication. New treatments with limited adverse events are in high demand for this unmet medical need. An effective peptide vaccine would represent an ideal candidate, since vaccines generally have very low levels of side effects.
This study will explore if vaccination against the immune checkpoint molecule PD-L1 leads to responses in patients with high risk smoldering myeloma. PD-L1 is thought to play a role in the rate of progression from smoldering myeloma to symptomatic myeloma. Targeting this pathway with little risk of adverse events would potentially prevent or delay progression to symptomatic myeloma.
- Conditions
- Smoldering Multiple Myeloma
- Being tested
- PD-L1 peptide
- Keywords
- smoldering, myeloma, vaccination, PD-L1, high-risk
- Medical subject headings
- Smoldering Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-L1 peptideBiological
Also called IO103
PD-L1 peptide (100 micrograms) emulsified with the adjuvant Montanide ISA-51 given subcutaneously 10 times every second week over the course of 26 weeks including a five-week break.
| Study group | Role | What they receive |
|---|---|---|
| Vaccination | Experimental | Vaccination with PD-L1 peptide Receives: Biological: PD-L1 peptide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Overall response rates (ORR) defined by IMWG criteria as PR+VGPR+CR+sCR during treatment and two weeks after end of treatment per patient.
Measured: Planned analysis cut-off per patient: two weeks after last vaccination.
Secondary outcomes (5)
Immunogenicity of the PD-L1 vaccine
Blood, skin biopsies and bone marrow samples will be assessed with ELISPOT assays for levels of immune response to the vaccine.
Measured: Samples taken before, during and two weeks after last vaccination.
Incidence of Treatment Emergent Adverse Events
Safety analysis will be conducted using the Safety Population defined as any patient receiving one dose of study treatment. For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate.
Measured: Planned analysis cut-off per patient: two weeks after last vaccination
Progression-free survival (PFS)
PFS from diagnosis is defined as the time from diagnosis to the disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free. This will be compared with published progression rates.
Measured: Planned analysis 2 years and 5 years post initiation of therapy.
Time to progression (TTP)
Time from diagnosis of SMM to progression to symptomatic myeloma compared to historical controls. Progression is defined as biochemical or diagnostic progression in accordance with the 2014 IMWG criteria for diagnosis of multiple myeloma which includes the classic CRAB-criteria as well as: Clonal bone marrow plasma cell percentage ≥ 60%, Free light chain ratio ≥ 100 (Involved FLC level must be ≥ 100mg/L),> 1 focal lesion on MRI studies (at least 5 mm in size)
Measured: Planned analysis 2 years and 5 years post initiation of therapy.
Overall survival (OS)
OS from diagnosis is defined as the time from diagnosis to the death of the patient.
Measured: Planned analysis 2 years and 5 years post initiation of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2019
- Study start18 Feb 2019
- Primary completion10 Mar 2021
- Study completion10 Mar 2021
Why it stopped: Insufficient recruitment within planned enrolmentperiod.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoldering 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lene Meldgaard Knudsen
- Sponsor type
- University, hospital or other
- Collaborators
- IO Biotech
- Responsible party
- Sponsor-investigator, Lene Meldgaard Knudsen, Herlev Hospital
- Investigators
- Nicolai Jørgensen, MD, Principal investigator, Department of Hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03850522
- Sponsor's protocol ID
- MY18H2
- Other IDs
- 2018-003990-93, 2018
- Status last verified
- Apr 2022
- First submitted
- 19 Feb 2019
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Trial of PD-L1 Peptide Vaccination as Monotherapy in High Risk Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03850522
- Acronym / sponsor ID
- MY18H2
- Conditions
- Smoldering Multiple Myeloma
- Keywords
- smoldering, myeloma, vaccination, PD-L1, high-risk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient recruitment within planned enrolmentperiod.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Lene Meldgaard KnudsenUniversity, hospital or other
- Collaborators
- IO Biotech
- Study start
- 18 Feb 2019 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 10 Mar 2021 (actual)
- First posted
- 21 Feb 2019 (actual)
- 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 evaluating a new vaccine against PD-L1 as a possible treatment for high-risk smoldering multiple myeloma.
Detailed description
Smoldering multiple myeloma is an asymptomatic disorder with an annual risk of 10% of progression to the incurable cancer multiple myeloma. While many patients live for many years without progression, high risk patients have a median risk of progression of 29 months. No therapy has been approved for this indication. New treatments with limited adverse events are in high demand for this unmet medical need. An effective peptide vaccine would represent an ideal candidate, since vaccines generally have very low levels of side effects.
This study will explore if vaccination against the immune checkpoint molecule PD-L1 leads to responses in patients with high risk smoldering myeloma. PD-L1 is thought to play a role in the rate of progression from smoldering myeloma to symptomatic myeloma. Targeting this pathway with little risk of adverse events would potentially prevent or delay progression to symptomatic myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaccination | Experimental | Biological: PD-L1 peptideVaccination with PD-L1 peptide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003)
- High risk of progression to symptomatic multiple myeloma defined by the presence of ≥ 2 of the risk factors below:
- Age ≥18 years
- Performance status ≤ 2 (ECOG-scale)
- Expected survival > 3 months
Key exclusion criteria (23 listed)
- Non-secretory myeloma
- Patients fulfilling CRAB criteria:
- 1. s-Ca-ion >1,40 mmol/L, attributable to myeloma ii. R: Renal failure
- Evidence of myeloma defining events i. Clonal bone marrow plasma cell percentage ≥ 60% ii. Ratio of involved/uninvolved serum free light chain ratio ≥ 100 iii. >1 focal lesions on MRI studies, if clinically indicated
- Plasma cell leukemia
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 |
|---|---|---|
| PD-L1 peptideAlso: IO103PD-L1 peptide (100 micrograms) emulsified with the adjuvant Montanide ISA-51 given subcutaneously 10 times every second week over the course of 26 weeks including a five-week break. | Biological | Vaccination |
Primary outcome
Overall response rate
Time frame: Planned analysis cut-off per patient: two weeks after last vaccination.
Overall response rates (ORR) defined by IMWG criteria as PR+VGPR+CR+sCR during treatment and two weeks after end of treatment per patient.
5 secondary outcomes
Immunogenicity of the PD-L1 vaccine
Time frame: Samples taken before, during and two weeks after last vaccination.
Incidence of Treatment Emergent Adverse Events
Time frame: Planned analysis cut-off per patient: two weeks after last vaccination
Progression-free survival (PFS)
Time frame: Planned analysis 2 years and 5 years post initiation of therapy.
Time to progression (TTP)
Time frame: Planned analysis 2 years and 5 years post initiation of therapy.
Overall survival (OS)
Time frame: Planned analysis 2 years and 5 years post initiation of therapy.
Results and safety
The study was stopped early (reason given: Insufficient recruitment within planned enrolmentperiod.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2022.
- Individual participant dataSharing planned: Undecided
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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.
Nicolai Jørgensen, MD principal investigator
Department of Hematology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-L1 peptide in people with Smoldering Multiple Myeloma, run by Lene Meldgaard Knudsen at 1 site in Denmark.
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 25 inclusion and 23 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 15 Apr 2022. 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 Denmark. 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 was stopped early (reason given: Insufficient recruitment within planned enrolmentperiod.). 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?
Overall response rate (time frame: Planned analysis cut-off per patient: two weeks after last vaccination.). 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 15 Apr 2022.