Chronic Lymphocytic LeukemiaPhase 1NCT04688385
Personalized Multi-peptide Vaccination in CLL Patients
A Phase 1 study testing Multipeptide Vaccine+ XS15 in people with Chronic Lymphocytic Leukemia, run by University Hospital Tuebingen at 2 sites in Germany.
Trial summary
The aim of this study is to evaluate the efficiency along with safety and toxicity of a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes. 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?
- Multipeptide Vaccine+ XS15
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesGermany
- Study dates
- 23 Dec 2020to 17 Oct 2024
- Phase
- Phase 1
- 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
- Documented diagnosis of CLL according to iWCLL guidelines
- For Screening phase:
- CLL that warrants treatment (according to modified criteria for initiation of therapy):
- Massive (ie, lower edge of spleen ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
- Massive (ie, ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
- Progressive lymphocytosis in the absence of infection, with an increase in blood ALC ≥ 50% over a 2-month period or lymphocyte doubling time of < 6 months (as long as initial ALC was ≥ 30,000/L), or
Show all 29Show fewer
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or -Constitutional symptoms, defined as any one or more of the following disease- related symptoms or signs occurring in the absence of evidence of infection:
- Unintentional weight loss of ≥ 10% within the previous 6 months, or
- Significant fatigue (≥ Grade 2), or
- Fevers > 38.0°C for ≥ 2 weeks, or
- Night sweats for > 1 month.
- Planned initiation of a ibrutinib-based regime (monotherapy or cominational therapy (e.g. anti-CD20))
- For Vaccination phase:
- Ongoing ibrutinib therapy (monotherapy).
- Achievement of a response (at least PR according to iWCLL guidelines)
- MRD positivity (CLL cells in peripheral blood ≥ 10-4, determined by flow cytometry, Labor Kiel, Prof. Brüggemann).
- Negative SARS-CoV-2 test (as long as WHO declares pandemic spread of SARS-CoV-2)
- Prior ibrutinib treatment of at least 6 months and not longer than 8 months.
- HLA typing positive for any of the following HLA alleles: HLA-A*02, A*24, B*07.
- Ability to understand and voluntarily sign an informed consent form.
- Ability to adhere to the study visit schedule and other protocol requirements.
- Age ≥ 18 years at the time of signing the informed consent form.
- ECOG performance status score of ≤ 2.
- Negative serological Hepatitis B test or negative PCR in case of positive serological test without evidence of an active infection, negative testing of Hepatitis C RNA, negative HIV test within 6 weeks prior to study inclusion.
- Female patients of childbearing potential (FCBP) and male volunteers with partners of child bearing potential, who are sexually active, must agree to the use of two effective forms (at least one highly effective method) of contraception. This should be started from the signing of the informed consent and continue throughout period of study
- Postmenopausal or evidence of non-childbearing status. For FCBP: negative urine or serum pregnancy test within 14 days prior to study treatment.
- Postmenopausal or evidence of non-childbearing status is defined as:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
- Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
Who cannot join
- Pregnant or lactating females.
- Treatment regimes without ibrutinib
- Ibrutinib-related side effects > CTC grade 2 (CTCAE V5.0)
- Participation in any clinical study or having taken any investigational therapy which would interfere with the study primary and secondary end points.
- Prior history of malignancies other than CLL, unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
- Basal cell carcinoma of the skin
Show all 14Show fewer
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
- Disease transformation (active), i.e. Richter's syndrome, prolymphocytic leukemia.
- Autoimmune hemolysis or immune thrombocytopenia caused by CLL
- Any immunosuppressive treatment not related to CLL except corticosteroids
- Pre-existing auto-immune disease except for Hashimoto thyroiditis and mild (not requiring immunosuppressive treatment) psoriasis
- Chronic lung disease requiring drug treatment
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University Hospital Tuebingen
Tübingen, Baden-Wurttemberg, 72076
university Hospital Tuebingen
Tübingen, 72076
About this study
Official title: IVAC-XS15-CLL01: Personalized Multi-peptide Vaccination in Combination with the TLR1/2 Ligand XS15 in CLL Patients Undergoing Ibrutinib-based Regimes
The aim of this study is to evaluate the efficiency along with safety and toxicity of a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes.
Read the detailed description
This is a phase I patient-individualized multi-peptide vaccination study in combination with the novel TLR1/2 ligand XS15 in CLL patients under ibrutinib treatment and based on the following rationale:
With the development and clinical success of targeted therapies, the treatment landscape for CLL, which is the most common leukemia in adults, has faced profound changes in the recent years. The disease control achieved by ibrutinib, an inhibitor of the Brutons tyrosine kinase (BTK), has led to its approval as first line therapy. However, in most cases only partial remissions are achieved, and so far perpetual ibrutinib treatment bearing the risk of side effects and development of drug resistance is required. Therefore, current efforts are focusing on the further reduction/elimination of residual CLL cells to allow for reduced treatment time as well as the achievement of long-lasting remissions. A rational and promising approach to achieve this goal is peptide-based immunotherapy, which represents a low side-effect treatment relying on specific immune recognition of tumor-associated HLA presented peptides. Several peptide vaccination studies have reported promising result in terms of in vivo immunogenicity, but so far lacked broad clinical responses. This likely is due to several so far unmet prerequisites for clinical effective peptide vaccination, including the selection of antigens, adjuvants, combinatorial drugs and vaccination time points.
The investigators here adresse these issues as follows:
The reportedly distorted relationship of gene expression and HLA-restricted presentation of the corresponding gene product requires direct methods for peptide target identification for vaccination approaches. This is realized by mass spectrometry-based analysis of the entirety of naturally presented HLA ligands, termed the HLA ligandome of cancer cells. In the recent years, the investigators worked intensively on the characterization of such TAA in HM based on the direct isolation of naturally presented HLA class I and II ligands from leukemia cells and the subsequent identification by mass spectrometry. To allow for the timely and cost-effective production of personalized vaccine cocktail for patients in clinical studies based on HLA ligandome analyses, the investigators have established a so called "warehouse concept" providing premanufactured highly frequent TAA for the formulation of personalized vaccine cocktails. The feasibility of such a warehouse concept, which is utilized in the iVAC-XS15-CLL01 study, was already proven by the investigator's first clinical peptide vaccination study (iVAC-CLL01, NCT02802943). The warehouse has been built based on comprehensive HLA ligandome analysis of CLL cells and composites of a modified cocktail used for the iVAC-CLL01 study as described above. On basis of the individual HLA allotype and a HLA ligandome analysis of CLL cells of the respective patient, 10 tumor-associated peptides are selected from the peptide warehouse. The so-called CLL peptide cocktails (drug substance) are designed to trigger the cellular part of the patients' immune system by activation of CLL-specific T cells. Once activated, these cells can destroy malignant cells presenting the respective antigens. Applying several CLL-associated antigens simultaneously increases the likelihood that a multi-clonal, broad and at the same time highly specific T-cell response is mounted, therebypreventing potential tumor escape mechanisms.
Besides the selection of optimal antigen targets, a further important prerequisite is the use of suitable adjuvant drugs capable to induce potent and long-lasting immune responses. The investigators will use the novel TLR1/2 ligand (XS15, developed in Tübingen) that (i) is water-soluble and (ii) GMP-amenable, (iii) non-toxic and (iv) effective in inducing T cells specific for peptides in vivo.
Another important factor for the clinical effectiveness of peptide-based immunotherapy is the rational combination with standard therapies. In this iVAC-XS15-CLL01 trial, peptide vaccination will be applied in CLL patients under ibrutinib treatment which have achieved at least a partial remission. The remission stage or, even better, the stage of MRD ensures an optimal effector to target cell ratio for peptide-based immunotherapy, as most of the tumor cells are eliminated and the T-cell compartment is recovered. Notably, several studies have proven that ibrutinib does not impair and even can show positive effects on T-cell response.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Multipeptide Vaccine+ XS15
- 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.
Multipeptide Vaccine+ XS15Biological
Peptide vaccination will take place in CLL patients that achieved at least a partial remission with detectable MRD after at least 6 and less than 9 months of an ibrutinib-based treatment regime. MRD will be determined by flow cytometry. MRD positivity is defined as > 10-4 CLL cells in peripheral blood or bone marrow. Patients will receive either ibrutinib monotherapy or combinational therapy before study treatment. Vaccination will be done under ibrutinib monotherapy (i.e. after the end of e.g. anti-CD20 treatment, if applicable).
| Study group | Role | What they receive |
|---|---|---|
| Multipeptide Vaccine + XS 15 | Experimental | a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes Receives: Biological: Multipeptide Vaccine+ XS15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Induction of a T-cell response after vaccination
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit.
Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Measured: Visit 2=Day 30 +/-7days
Induction of a T-cell response after vaccination on Visit 3
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit.
Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Measured: Visit 3= Day60 +/- 7days
Induction of a T-cell response after vaccination on Visit 4
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit.
Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Measured: Visit 4= 4 to 6 weeks after Visit 3
Induction of a T-cell response after vaccination on Visit 5
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit.
Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Measured: Visit 5 =6 months +/- 14 days after Visit 3
Secondary outcomes (6)
Immunophenotyping I on Baseline
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Baseline
Immunophenotyping I on Visit 1
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Visit 1=Day 1+/-7 days
Immunophenotyping I on Visit 2
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Visit 2=Day 30 +/-7days
Immunophenotyping I on Visit 3
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Visit 3= Day60 +/- 7days
Immunophenotyping I on Visit 4
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Visit 4= 4 to 6 weeks after Visit 3
Immunophenotyping I on Visit 5
- Characterization of vaccine induced T-cell responses from Baseline through follow-up: Phenotyping of peptide-specific T-cells by flow cytometry in [%]
Measured: Visit 5 =6 months +/- 14 days after Visit 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2020
- Study start23 Dec 2020
- Primary completion17 Oct 2024
- Study completion17 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- As usual in early phase 1 and 2 studies, statistical planning is designed as such that a statistically reasoned decision for or against a subsequent phase 3 study can be made. The sample size of the study was chosen based on the assumption that, in the case of peptide specific immune response induction in ≤ 30% of the patients, the therapy concept is extended with a probability of at most 5% (type one error, one-sided). On the other hand, in the case of peptide specific immune response induction in ≥ 60% of the patients, the therapy concept should be followed with a probability of at least 80% (power). With a sample size of n = 20 patients, this means that at least 10 patients must have an immune response, so that the therapy concept is evaluated in a randomized phase 3 study. The exact power is 87%, the exact type 1 error is 4.8% (calculations based on the binomial distribution with n = 20, p = 0.3 or p = 0.6, k \<10 or k ≥ 10).
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Helmut Salih, Prof.Dr., Study director, CCU Translational Immunology, University Hospital Tuebingen,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04688385
- Sponsor's protocol ID
- iVAC-XS15-CLL01
- Status last verified
- Nov 2024
- First submitted
- 8 Dec 2020
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Heitmann JS, Maringer Y, Jung S, Wacker M, Hackenbruch C, Polster M, Marconato M, Nelde A, Bauer J, Zwick M, Baur AS, Metzger A, Krolla C, Andrieux G, Kohler N, Boerries M, Denk M, Zieschang L, Kammer C, Hoenisch-Gravel N, Richter M, Oezbek MT, Wirths S, Dengler A, Dubbelaar ML, Pumptow M, Martus P, Bruggemann M, Rammensee HG, Salih HR, Walz JS. Personalised multipeptide-based T-cell activator for chronic lymphocytic leukaemia: an open-label, single-centre, phase 1 study. Lancet Haematol. 2026 Feb;13(2):e74-e85. doi: 10.1016/S2352-3026(25)00323-0. Epub 2026 Jan 14.
PubMed 41547362Nelde A, Maringer Y, Bilich T, Salih HR, Roerden M, Heitmann JS, Marcu A, Bauer J, Neidert MC, Denzlinger C, Illerhaus G, Aulitzky WE, Rammensee HG, Walz JS. Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia. Front Immunol. 2021 Jul 8;12:705974. doi: 10.3389/fimmu.2021.705974. eCollection 2021.
PubMed 34305947
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IVAC-XS15-CLL01: Personalized Multi-peptide Vaccination in Combination with the TLR1/2 Ligand XS15 in CLL Patients Undergoing Ibrutinib-based Regimes
- ClinicalTrials.gov ID
- NCT04688385
- Acronym / sponsor ID
- iVAC-XS15-CLL01
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 23 Dec 2020 (actual)
- Primary completion
- 17 Oct 2024 (actual)
- Study completion
- 17 Oct 2024 (actual)
- First posted
- 30 Dec 2020 (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.
The aim of this study is to evaluate the efficiency along with safety and toxicity of a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes.
Detailed description
This is a phase I patient-individualized multi-peptide vaccination study in combination with the novel TLR1/2 ligand XS15 in CLL patients under ibrutinib treatment and based on the following rationale:
With the development and clinical success of targeted therapies, the treatment landscape for CLL, which is the most common leukemia in adults, has faced profound changes in the recent years. The disease control achieved by ibrutinib, an inhibitor of the Brutons tyrosine kinase (BTK), has led to its approval as first line therapy. However, in most cases only partial remissions are achieved, and so far perpetual ibrutinib treatment bearing the risk of side effects and development of drug resistance is required. Therefore, current efforts are focusing on the further reduction/elimination of residual CLL cells to allow for reduced treatment time as well as the achievement of long-lasting remissions. A rational and promising approach to achieve this goal is peptide-based immunotherapy, which represents a low side-effect treatment relying on specific immune recognition of tumor-associated HLA presented peptides. Several peptide vaccination studies have reported promising result in terms of in vivo immunogenicity, but so far lacked broad clinical responses. This likely is due to several so far unmet prerequisites for clinical effective peptide vaccination, including the selection of antigens, adjuvants, combinatorial drugs and vaccination time points.
The investigators here adresse these issues as follows:
The reportedly distorted relationship of gene expression and HLA-restricted presentation of the corresponding gene product requires direct methods for peptide target identification for vaccination approaches. This is realized by mass spectrometry-based analysis of the entirety of naturally presented HLA ligands, termed the HLA ligandome of cancer cells. In the recent years, the investigators worked intensively on the characterization of such TAA in HM based on the direct isolation of naturally presented HLA class I and II ligands from leukemia cells and the subsequent identification by mass spectrometry. To allow for the timely and cost-effective production of personalized vaccine cocktail for patients in clinical studies based on HLA ligandome analyses, the investigators have established a so called "warehouse concept" providing premanufactured highly frequent TAA for the formulation of personalized vaccine cocktails. The feasibility of such a warehouse concept, which is utilized in the iVAC-XS15-CLL01 study, was already proven by the investigator's first clinical peptide vaccination study (iVAC-CLL01, NCT02802943). The warehouse has been built based on comprehensive HLA ligandome analysis of CLL cells and composites of a modified cocktail used for the iVAC-CLL01 study as described above. On basis of the individual HLA allotype and a HLA ligandome analysis of CLL cells of the respective patient, 10 tumor-associated peptides are selected from the peptide warehouse. The so-called CLL peptide cocktails (drug substance) are designed to trigger the cellular part of the patients' immune system by activation of CLL-specific T cells. Once activated, these cells can destroy malignant cells presenting the respective antigens. Applying several CLL-associated antigens simultaneously increases the likelihood that a multi-clonal, broad and at the same time highly specific T-cell response is mounted, therebypreventing potential tumor escape mechanisms.
Besides the selection of optimal antigen targets, a further important prerequisite is the use of suitable adjuvant drugs capable to induce potent and long-lasting immune responses. The investigators will use the novel TLR1/2 ligand (XS15, developed in Tübingen) that (i) is water-soluble and (ii) GMP-amenable, (iii) non-toxic and (iv) effective in inducing T cells specific for peptides in vivo.
Another important factor for the clinical effectiveness of peptide-based immunotherapy is the rational combination with standard therapies. In this iVAC-XS15-CLL01 trial, peptide vaccination will be applied in CLL patients under ibrutinib treatment which have achieved at least a partial remission. The remission stage or, even better, the stage of MRD ensures an optimal effector to target cell ratio for peptide-based immunotherapy, as most of the tumor cells are eliminated and the T-cell compartment is recovered. Notably, several studies have proven that ibrutinib does not impair and even can show positive effects on T-cell response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- As usual in early phase 1 and 2 studies, statistical planning is designed as such that a statistically reasoned decision for or against a subsequent phase 3 study can be made. The sample size of the study was chosen based on the assumption that, in the case of peptide specific immune response induction in ≤ 30% of the patients, the therapy concept is extended with a probability of at most 5% (type one error, one-sided). On the other hand, in the case of peptide specific immune response induction in ≥ 60% of the patients, the therapy concept should be followed with a probability of at least 80% (power). With a sample size of n = 20 patients, this means that at least 10 patients must have an immune response, so that the therapy concept is evaluated in a randomized phase 3 study. The exact power is 87%, the exact type 1 error is 4.8% (calculations based on the binomial distribution with n = 20, p = 0.3 or p = 0.6, k <10 or k ≥ 10).
| Arm | Type | Receives |
|---|---|---|
| Multipeptide Vaccine + XS 15 | Experimental | Biological: Multipeptide Vaccine+ XS15a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Documented diagnosis of CLL according to iWCLL guidelines
- CLL that warrants treatment (according to modified criteria for initiation of therapy):
- Massive (ie, lower edge of spleen ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
- Massive (ie, ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
- Progressive lymphocytosis in the absence of infection, with an increase in blood ALC ≥ 50% over a 2-month period or lymphocyte doubling time of < 6 months (as long as initial ALC was ≥ 30,000/L), or
Key exclusion criteria (14 listed)
- Pregnant or lactating females.
- Treatment regimes without ibrutinib
- Ibrutinib-related side effects > CTC grade 2 (CTCAE V5.0)
- Participation in any clinical study or having taken any investigational therapy which would interfere with the study primary and secondary end points.
- Prior history of malignancies other than CLL, unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
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 |
|---|---|---|
| Multipeptide Vaccine+ XS15Peptide vaccination will take place in CLL patients that achieved at least a partial remission with detectable MRD after at least 6 and less than 9 months of an ibrutinib-based treatment regime. MRD will be determined by flow cytometry. MRD positivity is defined as > 10-4 CLL cells in peripheral blood or bone marrow. Patients will receive either ibrutinib monotherapy or combinational therapy before study treatment. Vaccination will be done under ibrutinib monotherapy (i.e. after the end of e.g. anti-CD20 treatment, if applicable). | Biological | Multipeptide Vaccine + XS 15 |
Primary outcome
Induction of a T-cell response after vaccination
Time frame: Visit 2=Day 30 +/-7days
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit. Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Induction of a T-cell response after vaccination on Visit 3
Time frame: Visit 3= Day60 +/- 7days
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit. Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Induction of a T-cell response after vaccination on Visit 4
Time frame: Visit 4= 4 to 6 weeks after Visit 3
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit. Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
Induction of a T-cell response after vaccination on Visit 5
Time frame: Visit 5 =6 months +/- 14 days after Visit 3
60ml of heparin blood for immunomonitoring and analysis of peptide specific T-cell response will be analyzed by the Walz lab, KKE Translational Immunology at the the Department of Immunology, Tübingen (central laboratory). Blood will be taken prior to peptide vaccination on V1, V2, V3, at the end of study visit and the follow up visit. Induction of a T-cell response after vaccination on Visit 2, 3, 4 and 5 (follow-up) compared to baseline as determined by IFNγ ELISPOT.
6 secondary outcomes
Immunophenotyping I on Baseline
Time frame: Baseline
Immunophenotyping I on Visit 1
Time frame: Visit 1=Day 1+/-7 days
Immunophenotyping I on Visit 2
Time frame: Visit 2=Day 30 +/-7days
Immunophenotyping I on Visit 3
Time frame: Visit 3= Day60 +/- 7days
Immunophenotyping I on Visit 4
Time frame: Visit 4= 4 to 6 weeks after Visit 3
Immunophenotyping I on Visit 5
Time frame: Visit 5 =6 months +/- 14 days after Visit 3
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 9 Dec 2024.
- Derived from this study: PubMed 41547362Heitmann JS, Maringer Y, Jung S, Wacker M, Hackenbruch C, Polster M, Marconato M, Nelde A, Bauer J, Zwick M, Baur AS, Metzger A, Krolla C, Andrieux G, Kohler N, Boerries M, Denk M, Zieschang L, Kammer C, Hoenisch-Gravel N, Richter M, Oezbek MT, Wirths S, Dengler A, Dubbelaar ML, Pumptow M, Martus P, Bruggemann M, Rammensee HG, Salih HR, Walz JS. Personalised multipeptide-based T-cell activator for chronic lymphocytic leukaemia: an open-label, single-centre, phase 1 study. Lancet Haematol. 2026 Feb;13(2):e74-e85. doi: 10.1016/S2352-3026(25)00323-0. Epub 2026 Jan 14.
- Derived from this study: PubMed 34305947Nelde A, Maringer Y, Bilich T, Salih HR, Roerden M, Heitmann JS, Marcu A, Bauer J, Neidert MC, Denzlinger C, Illerhaus G, Aulitzky WE, Rammensee HG, Walz JS. Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia. Front Immunol. 2021 Jul 8;12:705974. doi: 10.3389/fimmu.2021.705974. eCollection 2021.
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Leukemia, Lymphocytic, Chronic, B-Cell
RecruitingPhase 2
Phase II Study of Combined Pirtobrutinib, Venetoclax and Obinutuzumab (PVO) Time-limited Treatment for Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia (SLL)
Active, not recruitingPhase 3
A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Leukemia, Lymphocytic, Chronic, B-Cell
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.
Helmut Salih, Prof.Dr. study director
CCU Translational Immunology, University Hospital Tuebingen,
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Multipeptide Vaccine+ XS15 in people with Chronic Lymphocytic Leukemia, run by University Hospital Tuebingen at 2 sites in Germany.
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 29 inclusion and 14 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 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Induction of a T-cell response after vaccination (time frame: Visit 2=Day 30 +/-7days). The study lists 4 primary outcomes in all. 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 NCT04688385, which also lists 2 linked publications.
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 9 Dec 2024.