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)

• ClinicalTrials.gov Identifier: NCT04758533
• Recruitment Status: Recruiting
• First Posted: February 17, 2021
• Last Update Posted: August 26, 2021
• Sponsor: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Collaborator: Apices Soluciones S.L.
• Information provided by (Responsible Party): Mrs. Laura Aranzasti, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

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 (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 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: April 19, 2021
• Estimated Primary Completion Date: October 2024
• Estimated Study Completion Date: October 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Álvaro Lassaletta Atienza, MD; +34 91 5035938; alvaro.lassaletta@salud.madrid.org

Locations

Spain

Hospital Infantil Universitario Niño Jesús; Recruiting

Madrid, Spain, 28009

Contact: Álvaro Lassaletta Atienza, MD

Contact alvaro.lassaletta@salud.madrid.org

Principal Investigator: Álvaro Lassaletta Atienza, MD

Sponsors and Collaborators

Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Apices Soluciones S.L.

Investigators

• Study Chair: Álvaro Lassaletta Atienza, MD; Hospital Infantil Universitario Niño Jesús

More Information

• Responsible Party: Mrs. Laura Aranzasti, MD, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• ClinicalTrials.gov Identifier: NCT04758533
• Other Study ID Numbers: FIBHNJ-2020-01
• First Posted: February 17, 2021
• Last Update Posted: August 26, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mrs. Laura Aranzasti, Hospital Infantil Universitario Niño Jesús, Madrid, Spain:

Icovir-5; Mesenchymal stem cells; Medulloblastoma; Diffuse Intrinsic Pontine Glioma

Additional relevant MeSH terms:

Glioma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases