Multi-peptide Vaccination Adjuvanted With XS15 in Acute Myeloid Leukemia Patients

NCT06252584 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: AML-VAC-XS15-01
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this Phase I study is to evaluate the immunogenicity along with safety and toxicity as well as first efficacy of a multi-peptide vaccine adjuvanted with the TLR1/2 ligand XS15 emulsified in Montanide ISA 51 VG (AML-VAC-XS15) in AML patients who have achieved CR or CRi with first line treatment.

Conditions

Acute Myeloid Leukemia, Adult

Keywords

acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• immunogenicity

  Blood will be taken before peptide vaccination and during vaccination phase and follow-ups at each visit IFN-gamma ELISPOT Counts Percentage of patients with induction of an AML-VAC-XS15-specific specific T-cell response until End of study visit (EOS) compared to baseline as determined by IFNγ ELISPOT.

  Visit 1( Day 0); Visit 2 (Day 42); End of Treatment (Day 70); Follow-Up (Day160); Follow-Up 1(Day 188); Follow-Up 2 (Day 250)

Study Arms (1)

Multipeptide Vaccination

EXPERIMENTAL

The vaccine cocktail will be administered subcutaneously (s.c.) together with the TLR1/2 ligand XS15 (50 μg) emulsified in Montanide ISA 51 VG (1:1) as adjuvant. Two vaccinations within a 6-week interval are planned, with the option of one additional booster in case of insufficient response after the first two vaccinations. Peptide vaccination will take place in AML patients that have achieved a morphological complete remission (CR) or a complete remission with incomplete blood count recovery (CRi) with standard first line treatment. MRD positivity is permitted. Vaccination will start 4-28 weeks after last application of intensive chemotherapy). Any maintenance treatment, e.g. with oral azacytidine or midostaurin, or ongoing low intensity therapy, e.g. with HMA, venetoclax etc. is permitted, can be applied throughout the vaccination and continued after study treatment according to the treating physician's decision.

Drug: Vaccines, Peptide

Interventions

Vaccines, Peptide DRUG

Multi-peptide vaccine cocktail comprising 9 different immunopeptidome-defined mutated and non-mutated AML/ leukemia stem and progenitor cell (LSC)-associated HLA class I and HLA class II peptides. The vaccine cocktail is synthesized and formulated in the GMP-certified Wirkstoffpeptidlabor at the University of Tübingen.

Also known as: Multipeptide Vaccine AML-VAC-XS15

Multipeptide Vaccination

Eligibility Criteria

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

You may qualify if:

• Males or females aged ≥18 years of age
• Existence of a written informed consent
• Documented diagnosis of AML according to WHO guidelines
• morphological complete remission (CR) or complete remission with incomplete blood count recovery (CRi)
• positive MRD is permitted
• completion of previous intensive therapy (first vaccination 4-28 weeks after last application of chemotherapy) or
• ongoing low intensity treatment with e.g. hypomethylating agents (HMA), venetoclax, etc.
• ongoing maintenance treatment with e.g. oral azacytidine or midostaurin is permitted.
• not eligible for allogeneic stem cell transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
• Adequate organ function laboratory values.
• bilirubin ≤ 3 times upper limit range (exception isolated indirect hyperbilirubinemia (Morbus Gilbert-Meulengracht)).
• alanine aminotransferase (ALT) and aminotransferase (AST), ≤ 5 times upper limit range
• creatinine clearance GFR \> 30 ml/min (CKD-EPI)
• platelets \> 50.000/μl

You may not qualify if:

• Pregnant or breastfeeding.
• Unwilling or unable to follow the study schedule for any reason.
• Chemotherapy or other systemic therapy or radiotherapy, up to 14 days prior to the first dose of study drug (ongoing maintenance treatment or low intensity treatment is permitted).
• Concurrent or previous treatment within 28 days in another interventional clinical trial with an investigational anticancer therapy or any other investigational therapy, which would interfere with the study's primary and secondary endpoints.
• Major surgery within 28 days of dosing of study drug.
• Treatment with immunotherapy agents within 28 days of dosing of study drug.
• Diagnosis of acute promyelocytic leukemia (APL)
• Autoimmune disease that requires or has required treatment with systemic immunosuppressive treatments, except low dose corticosteroids (\< 10 mg/ day), in the past 1 year.
• Prior history of malignancies, other than AML/myelodysplastic syndrome (MDS), unless the subject has been free of the disease for
• ≥ 2 years. Exceptions include the following: basal cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, histological finding of prostate cancer of TNM stage T1
• Prior stem cell allograft or organ transplantation
• Ongoing or active infection (including SARS-CoV-2)
• Have received any live vaccination within 28 days prior to the first dose of AML-VAC-XS15.

Sponsors & Collaborators

• University Hospital Tuebingen: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Protein Subunit Vaccines

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures

Central Study Contacts

Juliane Walz, Prof. Dr.

CONTACT

+49 7071 29; kketi@med.uni-tuebingen.de

Helmuit Salih, Prof.Dr.

CONTACT

+49 7071 29; kketi@med.uni-tuebingen.de

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: Single Arm Treatment

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: May 2, 2024
• Primary Completion: May 2, 2026
• Study Completion (Estimated): November 2, 2026
• Last Updated: February 9, 2024

Record last verified: 2024-01