Clinical trial to assess the safety and efficacy of AloCELYVIR in children, adolescent and young adults with diffuse intrinsic pointine glioma or medulloblastoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jul 2021 → 9 Apr 2026

Decision date (initial)

2023-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fundación CRIS Contra el Cáncer · Fundación el Sueño de Vicky

External identifiers

EU CT number

2022-502516-37-00

EudraCT number

2020-004838-37

ClinicalTrials.gov

NCT04758533

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

1. To evaluate the safety of the combination of AloCelyvir and radiotherapy in patients with newly diagnosed DIPG.
2. To evaluate the safety of AloCelyvir in monotherapy in patients with progression/relapse in medulloblastoma.

Secondary objectives 8

1. 1. Measurement of antitumor activity (measured as objective response rate [complete response and partial response] of the combination/monotherapy)
2. 2. Feasibility of the combination/monotherapy
3. 3. Safety (expansion phase)
4. 4. Estimation of progression-free survival
5. 5. Estimation of overall survival
6. 6. To compare the progression-free survival and overall survival of cohort A and B with a historical cohort of newly diagnosed DIPG patients and with a historical cohort of patients with relapse medulloblastoma.
7. 7. To study the antiadenoviral immune response
8. 8. To Study the replication kinetics of Icovir-5

Conditions and MedDRA coding

Newly diagnosed Diffuse Intrinsic Pointine Glioma (DIPG) or Medulloblastoma in relapse/progression in children, adolescents and young adults.

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. INCLUSION CRITERIA COMMON TO THE TWO COHORTS 1. Patients aged 1 to ≤21 years.
2. 2. Written informed consent signed by the patient's legal representative and, if applicable, the minor (informed consent in patients 12 years of age or older).
3. 3. Measurable or evaluable disease according to RANO criteria.
4. 4. Appropriate functional status, organic function (renal, hepatic) and hematological values: - Lanksy and karnofsky functional status ≥50%. Patients who use a wheelchair due of tumor-associated paralysis will be considered as outpatients for functional status evaluation. - Haematology function: • Platelet count ≥75.000/μL (without support for 3 days) • Absolute neutrophil count (ANC) ≥500/ μL (without growth factor for 3 days) • Hemoglobin ≥ 8 g/dL (Transfusion allowed) o Liver and renal function • Glomerular filtration rate (GFR) (estimated by Schwartz ) >60 mL/min/1.73 m2 • Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) • Transaminases (GOT and GPT) ≤3 × the upper limit of normal (ULN). ≤ 5 times ULN for patients with hepatic metastasis.
5. 5. Patient able to comply with treatment and schedule of visits and assessments.
6. 6. Life expectancy of ≥8 weeks.
7. 7. Highly effective contraceptive methods (Pearl rate <1) for sexually active males and females of childbearing age (CTFG, Reccomendations related to contraception and pregnancy in clinical trials V 1.1 2020--15). A woman is considered to have reproductive potential, i.e., childbearing, when she has reached menarche through menopause, unless she is permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy
8. 8. Highly sensitive negative pregnancy test in blood or urine for childbearing females.
9. INCLUSION CRITERIA COMMON TO THE COHORT A 1. Patient with new DIPG diagnosis (clinical, radiological, or histological in case a biopsy was performed before being included in the study).
10. 2. Not having received previous treatment with radiotherapy or chemotherapy.
11. 3. Patient able to receive radiotherapy
12. INCLUSION CRITERIA FOR COHORT B 1. Patient diagnosed with relapsed and/or refractory medulloblastoma. Patients must have received at least surgery, radiation therapy and chemotherapy as part of standard treatment and have failed these treatments before they can participate in this study.
13. 2. To be recovered to ≤ G1 from the toxic effects according to CTCAE derived from the previous treatments, excluding ototoxicity, alopecia and peripheral neurotoxicity.

Exclusion criteria 3

1. EXCLUSION CRITERIA COMMON TO THE TWO COHORTS 1. Previous treatment with Celyvir or AloCelyvir. 2. Known active bacterial, viral, fungal or parasitic infection not controlled 3. Known active Hepatitis B or C virus or VIH infection. 4. If patients are treated with corticosteroids, they should be clinically stable and on stable or tapering doses of steroids for at least one week. 5. To be receiving another anti-cancer treatment not foreseen in this protocol or to anticipate receiving it during the patient's participation in the same concomitant with the experimental treatment 6. Clinically significant or uncontrolled serious active and past systemic diseases that may pose an added risk to the patient
2. EXCLUSION CRITERIA COMMON TO THE COHORT A 1. Spontaneous massive intratumoral bleeding. Patients with postoperative bleeding (in case of biopsy or surgery) may be included in the study provided that the bleeding is controlled. The same rule applies for other postoperative complications (infection, loss of cerebrospinal fluid, absence of wound closure, subdural collection ...) 2. Patients who have previously received radiotherapy to the brain stem for another malignancy
3. EXCLUSION CRITERIA COMMON TO THE COHORT B 1. Washout period respect to previous treatments: - At least two weeks since the last dose of chemotherapy. For patients receiving low-dose metronomic oral chemotherapy, this period is at least one week. - At least four weeks since the autologous hematopoietic stem cell transplant - At least two weeks since the last focal radiotherapy or six weeks in case of cranio-spinal radiotherapy. - At least 2 weeks or 5 half-lifes (whichever occurs first) since the last dose of a biological or investigational treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dose-Limiting Toxicities rate

Secondary endpoints 9

1. Objective response rate
2. Rate of patients meeting selection criteria who can receive at least one cycle of Alo-Celyvir
3. Progression-free survival
4. Overall survival
5. To compare the progression-free survival and overall survival of cohort A and B with a historical cohort of newly diagnosed DIPG patients and with a historical cohort of patients with relapse medulloblastoma
6. Adverse Events Rate
7. Kinetics of anti-Adenovirus serotype 5 antibody titers
8. Kinetics of the number of CD8 antiadenovirus T-lymphocytes
9. Kinetics of circulating adenoviral particles

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus

Sponsor organisation

Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus

Address

Avenida Menendez Pelayo 65

City

Madrid

Postcode

28009

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus

Contact name

APICES SOLUCIONES S.L, Clinical Operations Department

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus

Contact name

APICES SOLUCIONES S.L, Clinical Operations Department

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

Application history

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