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 (AloCELYVIR)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Intrinsic Pontine Glioma; Medulloblastoma, Childhood, Recurrent
• Intervention / Treatment: Biological: AloCELYVIR

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Álvaro Lassaletta Atienza, MD; Phone Number: +34 91 5035938; Email: alvaro.lassaletta@salud.madrid.org

Study Locations

• Spain
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Nino Jesus
    • Contact: Álvaro Lassaletta Atienza, MD
    • Contact: Email: alvaro.lassaletta@salud.madrid.org
    • Principal Investigator: Álvaro Lassaletta Atienza, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicities rate (DLTs)	Proportion of patients who has experienced a DLT	1 Month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Percentage of patients that achieve complete response or partial response according to RECIST 1.1 criteria	24 Months
Feasibility of the combination/monotherapy	Rate of patients meeting selection criteria who can receive at least one dose of AloCELYVIR	1 Month
Incidence of treatment-Emergent Adverse Event	Rate of related-AEs	2,5 Months
Progression-free survival (PFS)	Time from the date of first dose of study treatment to the date of progression or death (from ant cause).	24 Months
Overall Survival (OS)	Time from the date of first dose of study treatment to the date of death	24 Months
Antiadenoviral humoral immune response in patients	Anti-Adenovirus serotype 5 antibody titers	2,5 Months
Antiadenoviral tumoral immune response in patients	Number of CD8 antiadenovirus T-lymphocytes	2,5 Months
Replication kinetics of Icovir-5	Quantification of circulating adenoviral particles	2,5 Months

Collaborators and Investigators

• Sponsor: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Collaborators: Apices Soluciones S.L.
• Investigators: Study Chair: Álvaro Lassaletta Atienza, MD, Hospital Infantil Universitario Nino Jesus

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Medulloblastoma; Mesenchymal stem cells; Diffuse Intrinsic Pontine Glioma; Icovir-5
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neuroectodermal Tumors, Primitive; Brain Stem Neoplasms; Infratentorial Neoplasms; Glioma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma
• Other Study ID Numbers: FIBHNJ-2020-01; 2020-004838-37 (EudraCT Number); EUCT Number:2022-502516-37-00 (Other Identifier: EMA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No