Smoldering Multiple Myeloma
Conditions
Keywords
smoldering, myeloma, vaccination, PD-L1, high-risk
Brief summary
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.
Interventions
BIOLOGICALPD-L1 peptide
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.
Sponsors
IO Biotech
Lene Meldgaard Knudsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003) 1. Serum M-component \>30g/L and/or 2. Urine M-component ≥ 500mg/24 hours and/or 3. ≥10% clonal plasma cells in bone marrow 4. 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: * 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. 1. ALAT \< 2.5 upper normal limit, i.e. ALAT \<112 U/l 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of the PD-L1 vaccine | Samples taken before, during and two weeks after last vaccination. | Blood, skin biopsies and bone marrow samples will be assessed with ELISPOT assays for levels of immune response to the vaccine. |
| Incidence of Treatment Emergent Adverse Events | Planned analysis cut-off per patient: two weeks after last vaccination | 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. |
| Time to progression (TTP) | Planned analysis 2 years and 5 years post initiation of therapy. | 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) |
| Overall survival (OS) | Planned analysis 2 years and 5 years post initiation of therapy. | OS from diagnosis is defined as the time from diagnosis to the death of the patient. |
| Progression-free survival (PFS) | Planned analysis 2 years and 5 years post initiation of therapy. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (QoL) | Baseline and up to two weeks after last vaccination | measured by change in European Organization for Research and Treatment of Cancer (EORTC) QLQ-30. |
Countries
Denmark
Outcome results
None listed