Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
42
Countries
1
Sites
2
Patients with acute myeloid leukemia or myelodysplastic syndrome.
Evaluate the efficacy and safety of Monalizumab after Haplo-SCT with PT-Cy.
Key facts
- Sponsor
- Humanitas Mirasole S.p.A.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 22 Jul 2022 → ongoing
- Decision date (initial)
- 2024-10-07
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Associazione AIRC nell’ambito del Bando Investigator Grant per l’anno 2018
External identifiers
- EU CT number
- 2024-516974-31-00
- EudraCT number
- 2020-005902-24
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Dose response
Evaluate the efficacy and safety of Monalizumab after Haplo-SCT with PT-Cy.
Secondary objectives 1
- Evaluate the effect of monalizumab on the immunological reconstitution and other clinical parameters of survival and toxicity.
Conditions and MedDRA coding
Patients with acute myeloid leukemia or myelodysplastic syndrome.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10000886 | Acute myeloid leukemia | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Patients capable of providing informed consent according to ICH/ GCP, and national/local regulations and be willing to comply with all study-related procedures.
- Adult patients aged =18 yearsold, without any restriction of gender and race.
- Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia or Myelodysplastic Syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN).
- Patients lacking a human leukocyte antigen (HLA) identical donor and receiving Haplo- SCT with GVHD/host versus graft (HVG) prophylaxis consisting of Cyclophosphamide: 40 or 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5, Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +35.
- Patient who have received Haplo-SCT with a myeloablative (MA) or reduced intensity (RIC) or non-myeloblative (NMA) conditioning followed either by a bone marrow or a peripheral blood stem cell (PBSC) graft.
- Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential.
- Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the last dose of study therapy. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the patient receives his last dose of study therapy contraception.
Exclusion criteria 8
- Patients aged < 18.
- Active uncontrolled infections.
- Central nervous system (CNS) involvement of AML disease.
- Karnofsky performance status (KPS) <60% or severe organ dysfunction, including a left ventricular ejection fraction <40%, DLCO <50% or creatinine clearance <50 ml/min (as per transplant eligibility).
- Pregnant or breast-feeding or intending to become pregnant during the study.
- Patients who rapidly relapse after allogenic-SCT before day 30 after Haplo-SCT.
- Patients who experience acute GVHD before day +30 after Haplo-SCT.
- Patients treated with a second allogeneic Allo-SCT.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- To evaluate the efficacy and safety of NKG2A blockade by Monalizumab after Haplo-SCT with PTCy in terms of GPFS.
Secondary endpoints 2
- Clinical Objectives: Evaluate the incidence of OS, PFS, NRM and post-transplant viral infections in patients receiving Monalizumab after Haplo-SCT.
- Biological Objectives: Evaluate the reconstitution and alloreactive functions of NK cell population against leukemic cells after Monalizumab administration.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10970031 · Product
- Active substance
- Monalizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 2 mg/kg milligram(s)/kilogram
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- ASTRAZENECA AB
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Humanitas Mirasole S.p.A.
- Sponsor organisation
- Humanitas Mirasole S.p.A.
- Address
- Via Alessandro Manzoni 56
- City
- Rozzano
- Postcode
- 20089
- Country
- Italy
Scientific contact point
- Organisation
- Humanitas Mirasole S.p.A.
- Contact name
- Immunologia Clinica
Public contact point
- Organisation
- Humanitas Mirasole S.p.A.
- Contact name
- Immunologia Clinica
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 42 | 2 |
| 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 | 2022-07-22 | 2022-07-22 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol_2024-516974-31-00 | 3.0 |
| Protocol (for publication) | D1_ Protocol_2024-516974-31-00 SoC | 3.0 |
| Protocol (for publication) | D1_ Protocol_2024-516974-31-00 TC | 3.0 |
| Protocol (for publication) | D1_ Protocol_2024-516974-31-00_letter | na |
| Protocol (for publication) | D1_ Protocol_2024-516974-31-00_PCL | na |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_donors | 1.1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_patients | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_patients TC | 2.0 |
| Subject information and informed consent form (for publication) | L2_GP letter | 1.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_2024-516974-31-00 | 3.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_2024-516974-31-00_ITA | 3.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_2024-516974-31-00_ITA TC | 3.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-20 | Italy | Acceptable 2024-10-02
|
2024-10-07 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-01-13 | Italy | Acceptable 2025-02-25
|
2025-03-17 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-11-24 | Italy | Acceptable 2025-02-25
|
2025-11-24 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2026-05-20 | Italy | Acceptable 2025-02-25
|
2026-05-20 |