iVAC-CLL01: Patient-individualized Peptide Vaccination After First Line Therapy of CLL

NCT02802943 | Completed Phase 2 DMC

• 1 other identifier: iVAC-CLL01:
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 5

Brief Summary

The aim of this study is to induce a peptide-specific immune response in CLL patients by multi-peptide vaccination with a patient-individualized peptide cocktail.

Conditions

Leukemia, Chronic Lymphatic

Keywords

CLL, Peptid Vaccination

Outcome Measures

Primary Outcomes (1)

• Induction of peptide-specific T cell responses

  The rate of patients with induction of peptide-specific T cell responses within a maximum of 6 month after start of therapy will be the primary endpoint for efficacy. Analysis of the primary endpoint= induction of immune response: The induction of peptide-specific T cell responses will be determined by IFNγ ELISPOT. T cell responses will be considered to be positive when \>15 spots/well (IFNγ ELISPOT) were counted and the mean spot count per well is at least 3-fold higher than the mean number of spots in the negative control wells (according to the cancer immunoguiding program guidelines).

  6 month after start of therapy

Secondary Outcomes (1)

• Overall Survival

  6 month after start of therapy

Study Arms (2)

Peptide Vaccine MRD +

EXPERIMENTAL

MRD-positive (MRD+) patients (flow cytometry based, CLL cells in peripheral blood or bone marrow ≥ 10-4 6-10 weeks after the end of first line treatment)

Biological: Peptide Vaccine; Drug: Imiquimod

Peptide Vaccine MRD-

EXPERIMENTAL

MRD-negative (MRD-) patients (flow cytometry based, CLL cells in peripheral blood and bone marrow \<10-4 6-10 weeks after the end of first line treatment)

Biological: Peptide Vaccine; Drug: Imiquimod

Interventions

Peptide Vaccine BIOLOGICAL

Individualized multi-peptide cocktail consisting of 300 μg each of 5 HLA class I and 4 HLA class II restricted peptides. The peptides for each individual patient will be selected from a warehouse consisting of 30 different peptides restricted by the 6 most common HLA class I allotypes (A\*01, A\*02, A\*03, A\*24, B\*07, B\*08) and 4 HLA class II peptides. Peptides will be administered subcutaneously. Vaccination will take place on d1, d4, d8, d15, d22 followed by vaccinations every 4 weeks for 1 year. The peptide warehouse is selected based on our data on the non-mutant HLA-presented antigenome of CLL identified as frequently presented CLL-associated T cell epitopes with a high potential for broad clinical application.

Peptide Vaccine MRD +; Peptide Vaccine MRD-

Imiquimod DRUG

All patients will receive imiquimod (Aldara®) as local adjuvant, applied topically at the side of vaccination 18h to 24h prior to the vaccination.

Peptide Vaccine MRD +; Peptide Vaccine MRD-

Eligibility Criteria

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

1. Documented diagnosis of CLL/SLL according to IWCLL guidelines. For Screening phase: * No pretreatment of CLL/SLL * Ability to mount an immune response: Positive immunresponse to EBV/CMV peptide mix (analyzed in 12 day recall IFNγ ELISPOT). For Vaccination phase: • Achievement of response (at least PR according to IWCLL guidelines) after first-line therapy according to treating physicians choice. 2. HLA typing positive for HLA alleles of peptides included in the warehouse with proven immunogenicity: HLA-A\*01, A\*02, A\*03, A\*24, B\*07, B\*08. 3. Ability to understand and voluntarily sign an informed consent form. 4. Age ≥ 18 years at the time of signing the informed consent form. 5. Ability to adhere to the study visit schedule and other protocol requirements. 6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2. 7. Negative serological Hepatitis B and C test or negative PCR in case of positive serological test without evidence of an active infection, negative HIV test within 6 weeks prior to randomization.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF): collaborator
• Klinikum Stuttgart: collaborator
• Marienhospital Stuttgart: collaborator
• Katharinenhospital Stuttgart: collaborator

Study Sites (5)

Katharinenhospital

Stuttgart, Baden-Wurttemberg, 70174, Germany

Location

Diakonie-Klinikum Stuttagrt

Stuttgart, Baden-Wurttemberg, 70176, Germany

Location

Marienhospital

Stuttgart, Baden-Wurttemberg, 70199, Germany

Location

Robert-Bosch-Krankenhaus Abteilung fuer Haematologie, Onkologie und Palliativmedizin

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Related Publications (1)

• Heitmann JS, Jung S, Wacker M, Maringer Y, Nelde A, Bauer J, Denk M, Hoenisch-Gravel N, Richter M, Oezbek MT, Dubbelaar ML, Bilich T, Pumptow M, Martus P, Illerhaus G, Denzlinger C, Steinbach F, Aulitzky WE, Muller MR, Dorfel D, Rammensee HG, Salih HR, Walz JS. Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients. Front Immunol. 2024 Nov 26;15:1482715. doi: 10.3389/fimmu.2024.1482715. eCollection 2024.

  PMID: 39660140 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Protein Subunit Vaccines; Imiquimod

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

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: MRD-negative (MRD-) patients (flow cytometry based, CLL cells in peripheral blood and bone marrow \<10-4 6-10 weeks after the end of first line treatment). MRD-positive (MRD+) patients (flow cytometry based, CLL cells in peripheral blood or bone marrow ≥ 10-4 6-10 weeks after the end of first line treatment)

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: June 16, 2016
• Study Start: October 5, 2016
• Primary Completion: September 30, 2022
• Study Completion: November 18, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

DE (5)