Newly diagnosed Diffuse Intrinsic Pointine Glioma (DIPG) or Medulloblastoma in relapse/progression in children, adolescents and young adults. MedDRA version: 21.0 Level: PT Classification code 10066594 Term: Medulloblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10080666 Term: Diffuse intrinsic pontine glioma System Organ Class: 10029104 - Neoplasms benign, malignant and un
Conditions
Interventions
Product Name: ALOCELYVIR
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Alogenic bone marrow stem adult mesenchymal cells expanded Infected with Icovir-5
Current Sponsor code: ICOVIR-
Sponsors
Fundación de Investigación Biomédica Hospital Niño Jesús
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: INCLUSION CRITERIA COMMON TO THE TWO COHORTS 1. Patients aged 1 to 21 years. 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: o 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. o 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 post-operative 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety of the combination of AloCelyvir and radiotherapy in patients with newly diagnosed DIPG. 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 (PFS) 5. Estimation of overall survival (OS) 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 in patients 8. To Study the replication kinetics of Icovir-5;Primary end point(s): 1. Dose-Limiting Toxicities rate (DLTs);Timepoint(s) of evaluation of this end point: 1. Every week during 4 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate 2. Rate of patients meeting selection criteria who can receive at least one cycle of Alo-Celyvir 3. Progression-free survival (PFS) 4. Overall survival 5. 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 6. Adverse Events Rate 7. Kinetics of anti-Adenovirus serotype 5 antibody titers 8. Kinetics of the number of CD8 antiadenovirus T-lymphocytes 9. Kinetics of circulating adenoviral particles;Timepoint(s) of evaluation of this end point: 1. Every 12 weeks since the start of treatment until disease progression. 2. Since the start of recruitment until the first dose of AloCelyvir. 3. Every 12 weeks since the start of treatment until disease progression. 4. Every 12 weeks since the start of treatment until death. 5. Every 12 weeks since the start of treatment until disease progression. 6. Every week during 8 weeks and at week 10 of study treatment. 7. Every week during 8 weeks and at week 10 of study treatment. 8. Every week during 8 weeks and at week 10 of study treatment. 9. Every week during 8 weeks and at week 10 of study treatment. | — |
Countries
Spain
Contacts
Public ContactClinical Operations Department
APICES SOLUCIONES S.L
Outcome results
None listed