Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
19
Countries
1
Sites
1
Patient affected by high risk Neuroblastoma relapsed or in progression after first line treatment.
To evaluate the safety and efficacy of haploidentical stem cell transplantation with alfa-beta-CD19+ depletion folowed by immunotherapy with donor-NK cells infusion and anti-GD2 moAb in patients with high risk Neuroblastoma relapsed or in progression disease after first line treatment.
Key facts
- Sponsor
- IRCCS Istituto Giannina Gaslini
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 29 Aug 2023 → ongoing
- Decision date (initial)
- 2025-01-31
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-519089-32-02
- EudraCT number
- 2022-000488-27
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate the safety and efficacy of haploidentical stem cell transplantation with alfa-beta-CD19+ depletion folowed by immunotherapy with donor-NK cells infusion and anti-GD2 moAb in patients with high risk Neuroblastoma relapsed or in progression disease after first line treatment.
Secondary objectives 3
- Chimerism and immunological reconstitution post TCRaß+CD19+ depleted haploidentical stem cell transplantation
- Antitumor activity of donor-derived NK-cells (graft-versus-tumor effect)
- Relevance of the donor NK cell selection criteria
Conditions and MedDRA coding
Patient affected by high risk Neuroblastoma relapsed or in progression after first line treatment.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10029260 | Neuroblastoma | 100000004864 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-519089-32-00 | TCRaß+CD19+ depleted haploidentical stem cell transplantation followed by immunotherapy in patients with relapsed/resistant high-risk neuroblastoma | IRCCS Istituto Giannina Gaslini |
| 2024-519089-32-01 | TCRaß+CD19+ depleted haploidentical stem cell transplantation followed by immunotherapy in patients with relapsed/resistant high-risk neuroblastoma | IRCCS Istituto Giannina Gaslini |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- High-risk neuroblastoma (stage 4 with age > 12 months at diagnosis, or stage 2, 3, 4s with MYCN amplification) in local, metastatic or combined recurrence after first-line therapy protocol
- Stabilization of disease (at or above STABLE DISEASE according to INRC criteria) achieved after salvage chemotherapy according to the center’s clinical practice
- Availability of a suitable HLA haploidentical familial donor to perform HSC donation from peripheral blood after stimulation with GCSF (+/-Plerixafor)
- Informed parental or legal guardian consent
Exclusion criteria 3
- Disease progressing after salvage therapy.
- Severe organ dysfunction, defined as grade 4 or higher dysfunctions according to international reference tables (CTCAE v 5.0).
- Life expectancy of less than 3 months.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Overall Survival (OS)
Secondary endpoints 12
- Engraftment and donor chimerism analysis
- Immune reconstitution (+30, +60, +90, +120, +180, +360)
- Infectious events
- Transplant-related mortality (TRM)
- Progression-free Survival (PFS)
- Early and late transplant-related toxicities
- Immunotherapy (antui-GD2 mAb)–related toxicities
- Donor-derived NK-cells infusion–related toxicities
- Disease response (INRC criteria)
- Acute and chronic GvHD
- Antitumor activity of donor-derived NK-cells (graft-versus-tumor effect)
- Relevance of the donor NK cell selection criteria
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD11677967 · Product
- Active substance
- Allogeneic Peripheral Blood-Derived Haematopoietic Stem Cells, Tcr Alpha/Beta+ CD19 Depleted
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10000 IU/Kg iu/kilogram
- Max total dose
- 10000 IU/Kg iu/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- IRCCS ISTITUTO GIANNINA GASLINI
- Paediatric formulation
- No
- Orphan designation
- No
Allogeneic peripheral blood-derived NK cells CD3- CD56+
PRD11689784 · Product
- Active substance
- Allogeneic Peripheral Blood-Derived Nk Cells CD3- CD56
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2000 IU/Kg iu/kilogram
- Max total dose
- 8000 IU/Kg iu/kilogram
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- IRCCS ISTITUTO GIANNINA GASLINI
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 6
Melfalan Tillomed 50 mg polvere e solvente per soluzione iniettabile/infusione
PRD9890550 · Product
- Active substance
- Melphalan
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 140 mg/m2 milligram(s)/square meter
- Max total dose
- 140 mg/m2 milligram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA03 — MELPHALAN
- Marketing authorisation
- 045006018
- MA holder
- TILLOMED ITALIA S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabina Accord 25 mg/ml Concentrato per soluzione iniettabile o per infusione
PRD2961173 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 40 mg/m2 milligram(s)/sq. meter
- Max total dose
- 160 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 043104013
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Grafalon 20 mg/ml concentrato per soluzione per infusione
PRD3161258 · Product
- Active substance
- Anti-T Lymphocyte Immunoglobulin for Human Use, Rabbit
- Substance synonyms
- LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN, RABBIT HUMAN T LYMPHOCYTE IMMUNOGLOBULIN, ANTI-HUMAN THYMOCYTE IMMUNOGLOBULIN, RABBIT
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 4 mg/Kg milligram(s)/kilogram
- Max total dose
- 12 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AA04 — ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)
- Marketing authorisation
- 042421014
- MA holder
- NEOVII BIOTECH GMBH
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Rixathon 100 mg concentrate for solution for infusion
PRD7932613 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/17/1185/001
- MA holder
- SANDOZ GMBH
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
TEPADINA 100 mg powder for concentrate for solution for infusion
PRD9801398 · Product
- Active substance
- Thiotepa
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10 mg/Kg milligram(s)/kilogram
- Max total dose
- 10 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AC01 — THIOTEPA
- Marketing authorisation
- EU/1/10/622/002
- MA holder
- ADIENNE S.R.L. S.U
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Qarziba 4.5 mg/mL concentrate for solution for infusion
PRD5240131 · Product
- Active substance
- Dinutuximab Beta
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10 mg/m2 milligram(s)/square meter
- Max total dose
- 500 mg/m2 milligram(s)/square meter
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01FX06 — -
- Marketing authorisation
- EU/1/17/1191/001
- MA holder
- RECORDATI NETHERLANDS B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
IRCCS Istituto Giannina Gaslini
- Sponsor organisation
- IRCCS Istituto Giannina Gaslini
- Address
- Via Gerolamo Gaslini 5
- City
- Genoa
- Postcode
- 16147
- Country
- Italy
Scientific contact point
- Organisation
- IRCCS Istituto Giannina Gaslini
- Contact name
- Stefano Giardino
Public contact point
- Organisation
- IRCCS Istituto Giannina Gaslini
- Contact name
- Stefano Giardino
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 19 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2023-08-29 | 2023-08-30 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 1 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 10 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 11 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 2 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 3 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 4 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 5 2024-519089-32-00 | 1 |
| Protocol (for publication) | D1_Protocol_ALLEGATO 9 2024-519089-32-00 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_placeholder | 1 |
| Subject information and informed consent form (for publication) | L1_Physician pratictioner | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents-guardian | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF postpuberal child | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF prepuberal child | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-20 | Italy | Acceptable 2025-01-21
|
2025-01-31 |