Clinical Trial to Assess the Safety and Efficacy of AloCELYVIR With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) in Combination With Radiotherapy or Medulloblastoma in Monotherapy

Sponsor

Hospital Infantil Universitario Niño Jesús, Madrid, Spain (Other)

Overall Status

Recruiting

CT.gov ID

NCT04758533

Collaborator

Apices Soluciones S.L. (Industry)

Enrollment

Location

Arm

41.4

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Intrinsic Pontine Glioma Medulloblastoma, Childhood, Recurrent	Biological: AloCELYVIR	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open, non-randomized, single-center Phase I clinical trial.Open, non-randomized, single-center Phase I clinical trial.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase IB Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy of AloCELYVIR (Mesenchymal Allogenic Cells + ICOVIR-5) in Children, Adolescent and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) in Combination With Radiotherapy or Medulloblastoma in Relapse/Progression in Monotherapy

Actual Study Start Date :

Apr 19, 2021

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AloCELYVIR Patients will received weekly infusion of AloCELYVIR during 8 weeks.	Biological: AloCELYVIR Mesenchymal allogenic cells + ICOVIR-5: 500.000 cells/kg

Arm

Intervention/Treatment

Experimental: AloCELYVIR

Patients will received weekly infusion of AloCELYVIR during 8 weeks.

Biological: AloCELYVIR

Mesenchymal allogenic cells + ICOVIR-5: 500.000 cells/kg

Outcome Measures

Primary Outcome Measures

Dose-Limiting Toxicities rate (DLTs) [1 Month]
Proportion of patients who has experienced a DLT

Secondary Outcome Measures

Objective response rate [24 Months]
Percentage of patients that achieve complete response or partial response according to RECIST 1.1 criteria
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).
Overall Survival (OS) [24 Months]
Time from the date of first dose of study treatment to the date of death
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA COMMON TO THE TWO COHORTS

Patients aged 1 to 21 years.
Written informed consent signed by the patients legal representative and, if applicable, the minor (informed consent in patients 12 years of age or older).
Measurable or evaluable disease according to RANO criteria.
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.

Patient able to comply with treatment and schedule of visits and assessments
Life expectancy of ≥8 weeks.
Appropriate contraceptive methods for sexually active males and females of childbearing age
Negative pregnancy test in blood or urine for females of childbearing age

INCLUSION CRITERIA COMMON TO THE COHORT A

Patient with new DIPG diagnosis (clinical, radiological, or histological in case a biopsy was performed before being included in the study).
Not having received previous treatment with radiotherapy or chemotherapy.
Patient able to receive radiotherapy

INCLUSION CRITERIA COMMON TO THE COHORT B

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.
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

Previous treatment with CELYVIR or AloCELYVIR.
Known active bacterial, viral, fungal or parasitic infection not controlled
Known active Hepatitis B or C virus or VIH infection.
If patients are treated with corticosteroids, they should be clinically stable and on stable or tapering doses of steroids for at least one week.
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.
Clinically significant or uncontrolled serious active and past systemic diseases that may pose an added risk to the patient

EXCLUSION CRITERIA COMMON TO THE COHORT A

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 ...)
Patients who have previously received radiotherapy to the brain stem for another malignancy

EXCLUSION CRITERIA COMMON TO THE COHORT B

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.