Personalized Multi-peptide Vaccination in CLL Patients

NCT04688385 | Completed Phase 1 DMC

• 1 other identifier: iVAC-XS15-CLL01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Visit 5 =6 months +/- 14 days after Visit 3

Secondary Outcomes (6)

• Immunophenotyping I on Baseline

  Baseline

• Immunophenotyping I on Visit 1

  Visit 1=Day 1+/-7 days

• Immunophenotyping I on Visit 2

  Visit 2=Day 30 +/-7days

• Immunophenotyping I on Visit 3

  Visit 3= Day60 +/- 7days

• Immunophenotyping I on Visit 4

  Visit 4= 4 to 6 weeks after Visit 3

Study Arms (1)

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

Biological: Multipeptide Vaccine+ XS15

Interventions

Multipeptide Vaccine+ XS15 BIOLOGICAL

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).

Multipeptide Vaccine + XS 15

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (2)

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

university Hospital Tuebingen

Tübingen, 72076, Germany

Location

Related Publications (2)

• Heitmann JS, Maringer Y, Jung S, Wacker M, Hackenbruch C, Polster M, Marconato M, Nelde A, Bauer J, Zwick M, Baur AS, Lehmann 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 Jan 14:S2352-3026(25)00323-0. doi: 10.1016/S2352-3026(25)00323-0. Online ahead of print.

  PMID: 41547362 DERIVED

• Nelde 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.

  PMID: 34305947 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Helmut Salih, Prof.Dr.

  CCU Translational Immunology, University Hospital Tuebingen,

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 30, 2020
• Study Start: December 23, 2020
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-11

Locations

DE (2)