Clinical trial NCT03850522: PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma
Official title: Phase IIa Trial of PD-L1 Peptide Vaccination as Monotherapy in High Risk Smoldering Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Smoldering Multiple Myeloma
Keywords: smoldering
myeloma
vaccination
PD-L1
high-risk
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: IO Biotech
First posted: 2019-02-21
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Exclusion Criteria:

* Non-secretory myeloma
* Patients fulfilling CRAB criteria:

  i. C: Hypercalcemia,

  1. s-Ca-ion \>1,40 mmol/L, attributable to myeloma ii. R: Renal failure
  1. Estimated or measured creatinine clearance \<40ml/min, attributable to myeloma
  2. Increased s-creatinine, attributable to myeloma
  3. Decrease in estimated or measured creatinine clearance \<35% within a year, attributable to myeloma
  4. 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.

Primary outcomes:
measure: Overall response rate
timeFrame: Planned analysis cut-off per patient: two weeks after last vaccination.
Secondary outcomes:
measure: Immunogenicity of the PD-L1 vaccine
timeFrame: Samples taken before, during and two weeks after last vaccination.
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: Planned analysis cut-off per patient: two weeks after last vaccination
measure: Progression-free survival (PFS)
timeFrame: Planned analysis 2 years and 5 years post initiation of therapy.
measure: Time to progression (TTP)
timeFrame: Planned analysis 2 years and 5 years post initiation of therapy.
measure: Overall survival (OS)
timeFrame: Planned analysis 2 years and 5 years post initiation of therapy.
Other outcomes:
measure: Quality of Life (QoL)
timeFrame: Baseline and up to two weeks after last vaccination
measure: Quality of Life (QoL)
timeFrame: Baseline and up to two weeks after last vaccination
measure: Quality of Life (QoL)
timeFrame: Baseline and up to two weeks after last vaccination
Locations:
city: Herlev
country: Denmark
facility: Department of Hematology, Universityhospital Herlev and Gentofte
Study officials:
affiliation: Department of Hematology
name: Nicolai Jørgensen, MD
role: PRINCIPAL_INVESTIGATOR
References: