Diffuse Intrinsic Pontine Glioma, Medulloblastoma, Childhood, Recurrent
Conditions
Keywords
Icovir-5, Mesenchymal stem cells, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Brief summary
The aim of this study is to assess the safety and efficacy of AloCELYVIR, which consist in bone marrow-derived allogenic mesenchymal stem cells infected with an oncolytic Adenovirus, ICOVIR-5. It has recently been proven that this type of cells are able of transporting oncolytic substances to tumor targets that are difficult to reach, such as medulloblastomas and gliomas, youth cancers located in the cranial cavity that have a poor prognosis and a fatal outcome. In addition, to exerting an anti-tumor action, this virus has the ability to stimulate the immune response, making the therapy even more effective. Thus, the diffuse intrinsic pontine glioma and the medulloblastoma in relapse/progression have been chosen to study the potential of this new advanced therapy through a weekly infusion for 8 weeks.
Interventions
BIOLOGICALAloCELYVIR
Mesenchymal allogenic cells + ICOVIR-5: 500.000 cells/kg
Sponsors
Apices Soluciones S.L.
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open, non-randomized, single-center Phase I clinical trial.
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
COMMON TO THE TWO COHORTS 1. Patients aged 1 to 21 years. 2. Written informed consent signed by the patients legal representative and, if applicable, the minor (informed consent in patients 12 years of age or older). 3. Measurable or evaluable disease according to RANO criteria. 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) * 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. Patient able to comply with treatment and schedule of visits and assessments 6. Life expectancy of ≥8 weeks. 7. Appropriate contraceptive methods for sexually active males and females of childbearing age 8. Negative pregnancy test in blood or urine for females of childbearing age 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). 2. Not having received previous treatment with radiotherapy or chemotherapy. 3. Patient able to receive radiotherapy INCLUSION CRITERIA COMMON TO THE 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. 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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicities rate (DLTs) | 1 Month | Proportion of patients who has experienced a DLT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of the combination/monotherapy | 1 Month | Rate of patients meeting selection criteria who can receive at least one dose of AloCELYVIR |
| Incidence of treatment-Emergent Adverse Event | 2,5 Months | Rate of related-AEs |
| Progression-free survival (PFS) | 24 Months | Time from the date of first dose of study treatment to the date of progression or death (from ant cause). |
| Objective response rate | 24 Months | Percentage of patients that achieve complete response or partial response according to RECIST 1.1 criteria |
| Antiadenoviral humoral immune response in patients | 2,5 Months | Anti-Adenovirus serotype 5 antibody titers |
| Antiadenoviral tumoral immune response in patients | 2,5 Months | Number of CD8 antiadenovirus T-lymphocytes |
| Replication kinetics of Icovir-5 | 2,5 Months | Quantification of circulating adenoviral particles |
| Overall Survival (OS) | 24 Months | Time from the date of first dose of study treatment to the date of death |
Countries
Spain
Outcome results
None listed