Clinical trial to assess the safety and efficacy of AloCELYVIR in children, adolescent and young adults with diffuse intrinsic pointine glioma or medulloblastoma.
- Conditions
- ewly diagnosed Diffuse Intrinsic Pointine Glioma (DIPG) or Medulloblastoma in relapse/progression in children, adolescents and young adults.Therapeutic area: Diseases [C] - Neoplasms [C04]MedDRA version: 21.0Level: LLTClassification code: 10080666Term: Diffuse intrinsic pontine glioma Class: 10029104MedDRA version: 21.0Level: PTClassification code: 10066594Term: Medulloblastoma recurrent Class: 100000004864
- Registration Number
- CTIS2022-502516-37-00
- Lead Sponsor
- Fundacion Para La Investigacion Biomedica Hospital Infantil Universitario Nino Jesus
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 12
INCLUSION CRITERIA COMMON TO THE TWO COHORTS 1. Patients aged 1 to =21 years., 2. Not having received previous treatment with radiotherapy or chemotherapy., 3. 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., 2. To be recovered to = G1 from the toxic effects according to CTCAE derived from the previous treatments, excluding ototoxicity, alopecia and peripheral neurotoxicity., 2. 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)., 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) 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., 5. Patient able to comply with treatment and schedule of visits and assessments., 6. Life expectancy of =8 weeks., 7. 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, 8. 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).
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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To evaluate the safety of the combination of AloCelyvir and radiotherapy in patients with newly diagnosed DIPG.<br>2. To evaluate the safety of AloCelyvir in monotherapy in patients with progression/relapse in medulloblastoma.;Secondary Objective: 1. Measurement of antitumor activity (measured as objective response rate [complete response and partial response] of the combination/monotherapy), 2. Feasibility of the combination/monotherapy, 3. Safety (expansion phase), 4. Estimation of progression-free survival, 5. Estimation of overall survival, 6. To compare the progression-free survival and overall survival of cohort A and B with a historical cohort of newly diagnosed DIPG patients and with a historical cohort of patients with relapse medulloblastoma., 7. To study the antiadenoviral immune response, 8. To Study the replication kinetics of Icovir-5;Primary end point(s): Dose-Limiting Toxicities rate
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Objective response rate;Secondary end point(s):Rate of patients meeting selection criteria who can receive at least one cycle of Alo-Celyvir;Secondary end point(s):Progression-free survival;Secondary end point(s):Overall survival;Secondary end point(s):To compare the progression-free survival and overall survival of cohort A and B with a historical cohort of newly diagnosed DIPG patients and with a historical cohort of patients with relapse medulloblastoma;Secondary end point(s):Adverse Events Rate;Secondary end point(s):Kinetics of anti-Adenovirus serotype 5 antibody titers;Secondary end point(s):Kinetics of the number of CD8 antiadenovirus T-lymphocytes;Secondary end point(s):Kinetics of circulating adenoviral particles