Chronic Lymphocytic Leukemia
Conditions
Brief summary
This study is investigating the efficacy of PD-L1 and PD-L2 peptides in untreated CLL patients with unmutated IGHV gene status.
Detailed description
Chronic lymphocytic leukemia (CLL) is an incurable disease with the unmutated immunoglobulin heavy chain variable region (IGHV) gene status being an unfavorable prognostic marker. These patients have shorter time to first treatment which consist of toxic chemotherapy. Programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) are immune checkpoints hampering immune responses in many tumors including CLL. These proteins are expressed by suppressive bystander cells as well as CLL cells. Vaccinating subcutaneously with PD-L1 and PD-L2 peptides mobilises cytoxic T-cells specific towards PD-L1 and PD-L2 expressing cells. In this study we investigate if the PD-L1 and PD-L2 specific responses can overcome leukemic cells in CLL.
Interventions
COMBINATION_PRODUCTPD-L1, PD-L2 peptides with Montanide ISA51
PD-L1: 19 amino acid sequence from the PD-L1 protein; PD-L2: 21 amino acid sequence from the PD-L2 protein; The peptides are dissolved in dimethyl sulphoxide (DMSO) and mixed with Montanide.
Sponsors
IO Biotech
Lars Møller Pedersen
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
* CLL according to national guidelines (Lymphoma.dk). * Unmutated IGHV gene according to ERIC recommendations.(25) * No prior CLL directed treatment * Age ≥ 18 * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 * No life-threatening conditions * Adequate bone marrow function: Neutrophils \> 1,0 x 109/l; Platelets \> 100 x 109/l * Adequate renal function: Glomeruli filtration rate (eGFR)/1,73 m2 \> 50 mL/min * Adequate liver function: Aspartate Aminotransferase \< 100 U/L * For fertile 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.
Exclusion criteria
* Other active malignant diseases requiring treatment. * Significant medical condition per investigators judgement e.g. severe Asthma or chronic obstructive lung disease (COLD), poorly regulated heart condition, insulin dependent diabetes mellitus. * Acute or chronic viral/bacterial infection e.g. human immunodeficiency virus (HIV), Cytomegalo virus (CMV), Epstein-barr virus (EBV), hepatitis or tuberculosis * Serious known allergies or earlier anaphylactic reactions. * Known sensibility towards Montanide ISA51 * 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% * Psychiatric disorders that according to the investigator could influence compliance. * Treatment with other experimental drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response according to IW-CLL | 1 year | Progressive disease (PD), stable disease (SD), partial response (PR), complete response (CR) calculated on basis of changes in circulating lymphocytes and lymphnode/spleen/liver size according to criteria from the international working group on CLL (IW-CLL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune response by elispot | 1 year | T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release. |
| Grades of adverse events (AE) | 1 year | Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V. |
Countries
Denmark
Outcome results
None listed