Chronic Lymphocytic LeukemiaPhase 2NCT03939234
Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.
A Phase 2 study testing PD-L1, PD-L2 peptides with Montanide ISA51 in people with Chronic Lymphocytic Leukemia, run by Lars Møller Pedersen at 1 site in Denmark.
Trial summary
This study is investigating the efficacy of PD-L1 and PD-L2 peptides in untreated CLL patients with unmutated IGHV gene status. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- PD-L1, PD-L2 peptides with Montanide ISA51
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteDenmark
- Study dates
- 26 Apr 2019to 15 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
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
This study is investigating the efficacy of PD-L1 and PD-L2 peptides in untreated CLL patients with unmutated IGHV gene status.
Read the 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.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- PD-L1, PD-L2 peptides with Montanide ISA51
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-L1, PD-L2 peptides with Montanide ISA51Combination product
Also called IO103, IO120
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.
| Study group | Role | What they receive |
|---|---|---|
| Vaccination | Experimental | Untreated CLL patients with unmutated IgHV gene with a cut of at maximum of 2 % mutations. According to guidelines from the European Research Initiative on CLL (ERIC). Receives: Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response according to IW-CLL
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).
Measured: 1 year
Secondary outcomes (2)
Immune response by elispot
T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release.
Measured: 1 year
Grades of adverse events (AE)
Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start26 Apr 2019
- Primary completion15 Mar 2021
- Study completion15 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lars Møller Pedersen
- Sponsor type
- University, hospital or other
- Collaborators
- IO Biotech
- Responsible party
- Sponsor-investigator, Lars Møller Pedersen, Herlev Hospital
- Investigators
- Uffe M Klausen, MD, Principal investigator, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03939234
- Sponsor's protocol ID
- CLL19H1
- Other IDs
- 2018-004869-14, 2018
- Status last verified
- Feb 2022
- First submitted
- 3 May 2019
- Last updated
- 21 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Klausen U, Grauslund JH, Jorgensen NGD, Ahmad SM, Jonassen M, Weis-Banke SE, Martinenaite E, Pedersen LB, Lisle TL, Gang AO, Enggaard L, Hansen M, Holmstrom MO, Met O, Svane IM, Niemann CU, Pedersen LM, Andersen MH. Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV. Front Oncol. 2022 Nov 22;12:1023015. doi: 10.3389/fonc.2022.1023015. eCollection 2022.
PubMed 36483037
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.
- ClinicalTrials.gov ID
- NCT03939234
- Acronym / sponsor ID
- CLL19H1
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Lars Møller PedersenUniversity, hospital or other
- Collaborators
- IO Biotech
- Study start
- 26 Apr 2019 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 15 Mar 2021 (actual)
- First posted
- 6 May 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 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.
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 | Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51Untreated CLL patients with unmutated IgHV gene with a cut of at maximum of 2 % mutations. According to guidelines from the European Research Initiative on CLL (ERIC). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
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, PD-L2 peptides with Montanide ISA51Also: IO103, IO120PD-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. | Combination product | Vaccination |
Primary outcome
Clinical response according to IW-CLL
Time frame: 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).
2 secondary outcomes
Immune response by elispot
Time frame: 1 year
Grades of adverse events (AE)
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2022.
- Derived from this study: PubMed 36483037Klausen U, Grauslund JH, Jorgensen NGD, Ahmad SM, Jonassen M, Weis-Banke SE, Martinenaite E, Pedersen LB, Lisle TL, Gang AO, Enggaard L, Hansen M, Holmstrom MO, Met O, Svane IM, Niemann CU, Pedersen LM, Andersen MH. Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV. Front Oncol. 2022 Nov 22;12:1023015. doi: 10.3389/fonc.2022.1023015. eCollection 2022.
- Individual participant dataSharing planned: No
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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.
Uffe M Klausen, MD principal investigator
Herlev Hospital
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, PD-L2 peptides with Montanide ISA51 in people with Chronic Lymphocytic Leukemia, run by Lars Møller Pedersen 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 11 inclusion and 10 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: finished, as of the sponsor's last update on 21 Feb 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical response according to IW-CLL (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03939234, which also lists 1 linked publication.
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 21 Feb 2022.