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First-in-human Interleukin-15-transpresenting Wilms' Tumor Protein 1-targeting Autologous Dendritic Cell Vaccination in Cancer Patients (IL15-TransDC)

A

Antwerp University Hospital (UZA)

Status and phase

Active, not recruiting
Phase 2
Phase 1

Conditions

Esophageal Cancer
Pancreas Cancer
Ovarian Cancer
Liver Cancer

Treatments

Biological: IL15-transpresenting WT1-targeted Dendritic Cell Vaccine

Study type

Interventional

Funder types

Other

Identifiers

NCT05964361
CCRG19-001

Details and patient eligibility

About

The goal of this clinical trial is to investigate a new type of dendritic cell vaccine in patients with refractory or advanced solid tumors of the esophagus, liver, pancreas and ovaries. The main questions it aims to answer are:

  • is it feasible to produce and administer these dendritic cell vaccines?
  • is treatment with these dendritic cell vaccines safe?

Participants will first need to undergo a leukapheresis procedure to collect the cellular starting material for the dendritic cell vaccine production. The treatment consists of 6 vaccines, administered at biweekly intervals. Participants will be followed-up until 90 days after the last vaccine.

Full description

The investigational medicinal product concerns dendritic cells that were engineered to target the tumor antigen Wilms' Tumor-1 (WT1) and in addition transpresent the cytokine IL15 on their cell surface. By inclusion of the IL15-transpresentation mechanism, the intention is to render the dendritic cell more immunogenic (i.e. they have a higher capacity to stimulate the immune system to recognize and attack WT1-expressing cancer cells).

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Signed informed consent (i.e. date of study entry (T0))

  • Age ≥ 18 years at the time of signing informed consent

  • Diagnosis with a histologically or cytologically confirmed solid tumor of the pancreas, esophagus, liver or ovaries that is advanced, recurrent or progressing after at least first-line anti-cancer treatment, or for which no alternative standard therapy is available due to intolerance to or refusal of standard-of-care treatment.

  • Adequate hematological blood values following previous anti-cancer treatments, as judged by the Principal Investigator

  • All treatment-related toxicities must have resolved to CTCAE grade ≤ 2 or must be stable and well controlled with minimal, local or non-invasive intervention, as judged by the Principal Investigator

  • Reasonable life expectancy of at least 3 months, as estimated by the Principal Investigator

  • At least 1 measurable or evaluable lesion as defined by the latest version of Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines

  • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained at the time of screening:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support

    • Lymphocyte count ≥ 0.5 x 109/L (500/µL)

    • Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion

    • Hemoglobin ≥ 90 g/L (9 g/dL) (Patients may be transfused to meet this criterion)

    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions:

      • Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
      • Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
    • Total bilirubin ≤ 2 x ULN with the following exception:

      • Patients with known Gilbert disease: total bilirubin ≤ 3 x ULN
    • Creatinine ≤ 1.5 x ULN

    • Albumin ≥ 25 g/L (2.5 g/dL)

    • Phosphorus ≥ 0.78 mmol/L

  • World Health Organization (WHO) performance status 0-2

  • Willing or able to comply with the protocol, as judged by the Principal Investigator

  • Women of child bearing potential must have a negative serum or urine pregnancy test at the time of screening. Women of child bearing potential and men must agree to use effective contraception before, during and for at least hundred days after the last study treatment administration.

Exclusion criteria

  • Use of any investigational agent within 4 weeks before the planned day of leukapheresis

  • Corticosteroid treatment within 1 week before leukapheresis, unless the Principal Investigator rationalizes otherwise

  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.

    • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

      • Rash must cover < 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
  • Non-treated brain or meningeal mestases, or priorly treated brain or meningeal metastases with magnetic resonance imaging (MRI) evidence of progression in the last 8 weeks

  • Pregnant or breastfeeding. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until at least hundred days after the last study treatment administration

  • Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of the vaccine, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

Trial contacts and locations

1

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Central trial contact

CCRG Coordinating Center

Data sourced from clinicaltrials.gov

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