Combined antitumor therapy with ex vivo manipulated dendritic cells producing interleukin-12 in children, adolescents and young adults with progressive, recurrent or primarily metastatic high-risk tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Masarykova Univerzita

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Sep 2015 → 31 Jul 2024

Decision date (initial)

2024-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Masarykova univerzita · Nadační fond dětské onkologie Krtek

External identifiers

EU CT number

2024-516613-21-00

EudraCT number

2014-003388-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Assessment of safety of the autologous vaccine from dendritic cells producing interleukin-12 administered in combination therapy to patients with progressing, relapsing or primarily metastasing high-risk malignancies by the analysis of frequency of occurrence of AESI (adverse events of special interest) which are the primary combined safety endpoint.

Secondary objectives 2

1. Efficacy
2. Safety profile

Conditions and MedDRA coding

Progressive, recurrent or primarily metastatic high-risk paediatric malignancies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 1-25 years
2. Patient and/or his legal representatives has to sign the informed consent form
3. Histologically confirmed diagnosis of refractory or relapsing or primarily metastatic solid high-risk tumor of child type, treated according to standard methods. (The disease is defined as refractory in the case when the radiology response to 1st line treatment is steady disease, mixed response or progression. High risk is defined as a disease with anticipated 5-year survival less than 25% according to known and used standard methods of treatment.)
4. Performance status – defined according to Karnofsky or Lansky ≥ 50, which equals ECOG categories 0, 1 and 2. Karnofsky score will be used for patients > 10 years, Lansky score will be used for patients ≤ 10 years.
5. Anticipated survival ≥ 10 weeks.
6. Prior therapy: a) Patient must not currently have grade 3 and 4 (evaluated according podle CTCAE v4.0) of toxicity from the prior therapy, i. e. chemotherapy, surgery or radiotherapy or other protocol following treatment. b) Myelosuppressive therapy was finished at least 3 weeks before the planned sampling of tumor tissue. c) Biological treatment: Patient has to discotinue any biological (targeted) treatment at least 7 days before the planned sampling of the tumor tissue in the case of tyrosine kinase inhibitors or at least 3-fold of half life of the administered drug with the upper limit of 6 weeks. d) Immunosuppressive therapy: Patient has to discontinue the immunosuppressive drugs at least 3 weeks prior to tumor tissue sampling. e) Growth factors: should be discontinued at least 7 days prior to planned tumor tissue sampling. f) Patient should be able to undergo surgical procedure aimed at histological verification of refractory, relapsing or metastatic malignity with the objecitve of tumor tissue sampling for manufacture of the autologous dendritic cells vaccine. g) Radiotherapy should be discontinued at least 3 weeks prior to tumor tissue sampling. h) Transplantation: at least 3 months (12 weeks) from autologous transplantation or 6 months (26 weeks) from allogeneic transplantation.
7. Organ functions: a) Adequate bone marrow function defined as: absolute number of neutrofiles ≥ 0,75 thous./μl, thrombocytes ≥ 75 thous./μl (without support by transfusion), hemoglobin ≥ 80 g/l (without support by transfusion) or in patients with infiltration of bone marrow by their fundamental disease it may be defined as: absolute number of neutrophiles ≥ 0,5 thous./μl, thrombocytes ≥ 40 thous./μl (without support by transfusion), hemoglobin ≥ 80 g/l (without support by transfusion). b) Adequate kidney function defined as creatinine clearance GFR ≥ 70 mL/min/1.73 m2, serum creatinine up to maximally 1,5-fold of upper limit for the given age. c) Adequate liver function defined as bilirubin up to maximally 1,5-fold of upper limit for the given age, ALT a AST to maximally 2,5-fold of upper limit for the given age in patient without liver metastases, and up to maximally 5-fold of upper limit for the given age in patients liver metastases. d) Adequate heart function defined as fraction shortening ≥ 27% and ejection fraction ≥ 50% measured by echocardiography.
8. Female patients in fertile age must have negative results of pregnancy test.

Exclusion criteria 8

1. Patients with autoimmune disease that is not adequately treated.
2. Patients who have been treated by autologous dendritic cells vaccine within their prior treatment.
3. Patients with uncontrolled hypertension defined as follows: a) Patients aged ≤ 17 years – systolic and diastolic pressure is higher than 95 percentile for their height and age; b) Patients aged more than 17 years – systolic and diastolic pressure is ≥ 160/90 mmHg or just diastolic pressure ≥ 90 mmHg.
4. Pregnancy, lactation.
5. Patients with uncontrolled psychiatric diagnosis.
6. Patients with seropositivity: HIV1,2, Treponema pallidum, hepatitis B or hepatitis C.
7. Patients with known hypersensitivity to investigational medicinal product.
8. Patients who were involved in some other clinical trial on medicinal product within 30 days prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Combined primary endpoint of safety: frequency of events defined by the clinical trial protocol as AESI (adverse events of special interest)

Secondary endpoints 5

1. Time to progression
2. Overall survival
3. Objective response rate (RECIST)
4. Clinical benefit rate (CBR)
5. Frequency of all adverse events assessed in relation to type, seriousness and causality

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Masarykova Univerzita

Sponsor organisation

Masarykova Univerzita

Address

Zerotinovo Namesti 617/9, Brno-Mesto Brno-Mesto

City

Brno

Postcode

602 00

Country

Czechia

Scientific contact point

Organisation

Masarykova Univerzita

Contact name

Regina Demlová

Public contact point

Organisation

Masarykova Univerzita

Contact name

Regina Demlová

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications