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 pointine glioma (DIPG) in combination with radiotherapy or medulloblastoma in relapse/progression in monotherapy.
- Trial ID
- 2022-502516-37-00
- Protocol
- FIBHNJ-2020-01
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **safety** of AloCelyvir, a combination of allogenic bone marrow-derived mesenchymal stem cells transduced with Icovir-5, in conjunction with radiotherapy for patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Additionally, the trial aims to assess the safety of AloCelyvir as a monotherapy in patients experiencing progression or relapse of medulloblastoma. These evaluations are clinically relevant as they aim to establish the safety profile of AloCelyvir, which is crucial for determining its potential as a therapeutic option for these aggressive pediatric brain tumors.
Secondary objectives include:
- Measurement of antitumor activity, assessed by the objective response rate, including complete and partial responses, of the combination or monotherapy.
- Assessment of the feasibility of the combination or monotherapy.
- Evaluation of safety during the expansion phase.
- Estimation of progression-free survival and overall survival.
- Comparison of progression-free survival and overall survival of cohort A and B with historical cohorts of newly diagnosed DIPG patients and patients with relapsed medulloblastoma.
- Investigation of the antiadenoviral immune response.
- Study of the replication kinetics of Icovir-5.
Participants
The clinical trial involves a study population comprising **children, adolescents, and young adults** aged 1 to 21 years, diagnosed with either newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or medulloblastoma in relapse or progression. The trial includes both male and female participants, and the population is considered vulnerable due to the age and health conditions involved. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including not having received prior radiotherapy or chemotherapy, and having an appropriate functional status and organ function. Lifestyle considerations such as diet and physical activity are not specified. The trial aims to evaluate the safety of AloCelyvir in combination with radiotherapy for DIPG and as monotherapy for relapsed or progressive medulloblastoma. Key inclusion criteria include the ability to comply with treatment schedules and a life expectancy of at least eight weeks. Participants must also use highly effective contraceptive methods if of childbearing potential, and females must have a negative pregnancy test prior to participation.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and preliminary efficacy of AloCelyvir, a dispersion for infusion containing allogenic bone marrow-derived mesenchymal stem cells transduced with ICOVIR-5, in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or medulloblastoma in relapse or progression. This is a Phase IB, randomized, double-blind, controlled trial. The trial is expected to run from July 2021 to July 2025, with participant involvement lasting until the end of the study or until early termination criteria are met.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, previous treatment history, and functional status. The inclusion criteria specify that patients must be aged 1 to 21 years, have not received prior radiotherapy or chemotherapy, and have a life expectancy of at least eight weeks. The trial will include follow-up visits to monitor safety and efficacy endpoints, such as dose-limiting toxicities, objective response rate, and progression-free survival. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted.
Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the treatment regimen, or if the investigator deems it in the participant's best interest. The trial aims to compare the progression-free survival and overall survival of the study cohorts with historical cohorts of DIPG and medulloblastoma patients. The primary endpoint is the rate of dose-limiting toxicities, while secondary endpoints include adverse events rate and kinetics of anti-adenovirus serotype 5 antibody titers. The trial will ensure that all procedures adhere to ethical standards, with informed consent obtained from legal representatives and, where applicable, from the participants themselves.
Treatment
The clinical trial involves the administration of **AloCelyvir**, an experimental medication formulated as a **dispersion for infusion**. The active substance in AloCelyvir consists of **allogenic bone marrow-derived mesenchymal stem cells transduced with ICOVIR-5**, which are ex vivo expanded. This investigational product is administered via **intravenous infusion**. The trial aims to evaluate the safety, tolerability, and preliminary efficacy of AloCelyvir in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) in combination with radiotherapy, as well as in patients with medulloblastoma in relapse or progression as a monotherapy. The dosing schedule and frequency of administration are determined based on the specific protocol requirements for each patient cohort. Participant compliance is monitored through regular assessments and adherence checks as per the study protocol.
In addition to the experimental treatment, the study includes the use of **radiotherapy** as a non-experimental treatment for patients with newly diagnosed DIPG. Radiotherapy is administered according to standard-of-care practices and is combined with AloCelyvir to assess the safety of this combination therapy. For patients with medulloblastoma in relapse or progression, AloCelyvir is administered as a monotherapy without additional non-experimental treatments. The trial does not utilize a placebo or comparator treatment, focusing solely on the investigational product and its combination with radiotherapy where applicable. All treatments are conducted under strict clinical supervision to ensure participant safety and adherence to the study protocol.
Efficacy
Efficacy in this clinical trial will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the **Dose-Limiting Toxicities rate**, which will be used to evaluate the safety and tolerability of the treatment. Secondary endpoints include the **Objective response rate**, **Progression-free survival**, **Overall survival**, and the **Rate of patients meeting selection criteria who can receive at least one cycle of AloCelyvir**. Additionally, the trial will compare the progression-free survival and overall survival of cohort A and B with historical cohorts of newly diagnosed diffuse intrinsic pontine glioma (DIPG) patients and patients with relapsed medulloblastoma.
Further secondary endpoints involve the assessment of adverse events and the kinetics of specific immune responses, including the **Kinetics of anti-Adenovirus serotype 5 antibody titers**, **Kinetics of the number of CD8 antiadenovirus T-lymphocytes**, and **Kinetics of circulating adenoviral particles**. These parameters will be measured at predefined timepoints throughout the trial to provide a comprehensive evaluation of the treatment's efficacy and its impact on the disease progression and patient survival.
Inclusion and Exclusion Criteria
Inclusion Criteria
- INCLUSION CRITERIA COMMON TO THE TWO COHORTS 1. Patients aged 1 to ≤21 years.
- 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).
- 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) 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.
- Patient able to comply with treatment and schedule of visits and assessments.
- Life expectancy of ≥8 weeks.
- 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
- Highly sensitive negative pregnancy test in blood or urine for childbearing females.
- 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).
- Not having received previous treatment with radiotherapy or chemotherapy.
- Patient able to receive radiotherapy
- 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.
- 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
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 12 Jul 2021 | 12 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AloCelyvir | Test | DISPERSION FOR INFUSION | INTRAVENIOUS INFUSION | — | — | PRD10078578 |