E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk smoldering multiple myeloma. |
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E.1.1.1 | Medical condition in easily understood language |
High risk smoldering multiple myeloma. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075894 |
E.1.2 | Term | Smoldering myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of the phase IIa trial is to investigate the rate of response in patients with high risk smoldering multiple myeloma vaccinated with PD-L1 long1. |
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E.2.2 | Secondary objectives of the trial |
Furthermore, immunogenicity of the vaccine, adverse events, quality of life, time to progression and overall survival will be described. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥18 years • Smoldering multiple myeloma diagnosed < 5 years prior to inclusion • Performance status ≤ 2 (ECOG-scale) • High risk of progression to symptomatic multiple myeloma defined by the “Revised 2018 Mayo Criteria”1: o ≥ 2 of the risk factors below: Bone marrow Plasma Cells (BMPCs) ≥ 20% M-component > 2g/dL Free light chain (FLC) ratio > 20
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E.4 | Principal exclusion criteria |
• Non-secretory myeloma • 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. • 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. • 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
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E.5 End points |
E.5.1 | Primary end point(s) |
• Overall response rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Three months after last vaccination |
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E.5.2 | Secondary end point(s) |
• Immunogenicity of the vaccine (blood and bone marrow) • Incidence of treatment emergent adverse events (TEAE) and patient reported outcomes (PRO) in terms of quality of life (QoL) as well as patient reported adverse events (PRO-CTCAE) • Progression-free survival (PFS) • Time to progression (TTP) • Overall survival (OS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Analysis of Immunogenicity, PRO and Adverse events will be performed when the latest enrolled patient has been followed three months after last given vaccine. Analysis of TTP, PFS and OS will be performed at two time points of 48 months and 5 years from the inclusion of the latest enrolled patient.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |