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RECRUITING

NCT06892223

PHASE2

Anti-NKG2A Monoclonal Antibody for AML or MDS Patients Undergoing Haploidentical Transplantation

Sponsor: Istituto Clinico Humanitas

View on ClinicalTrials.gov

Summary

The goal of this clinical trial is to evaluate the effectiveness and safety of the anti-NKG2A monoclonal antibody (Monalizumab) in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The main questions this trial aims to answer are: * Does Monalizumab improve graft-versus-host disease-free and progression-free survival (GPFS) in patients after Haplo-SCT? * What are the safety and side effects of Monalizumab in this patient group? * How does Monalizumab affect the reconstitution and function of NK cells in patients undergoing Haplo-SCT? * Researchers will administer Monalizumab to participants on day +30 and +44 after transplantation to see if it enhances immune responses and prevents disease relapse or GVHD. Participants will: * Receive Monalizumab intravenously at 1 mg/kg on day +30 and day +44 after Haplo-SCT * Be monitored for clinical outcomes such as GVHD, survival rates, and immune function for up to one year after the transplant * Undergo regular checkups and tests to assess the effectiveness and safety of the treatment

Official title: Phase II Clinical Trial to Optimize the Dose of an Anti-NKG2A Monoclonal Antibody (humZ270 MAb, IPH2201) for Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Haploidentical Transplantation with Post- Transplantation Cyclophosphamide

Key Details

Gender

All

Age Range

18 Years - 99 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2021-12-03

Completion Date

2026-12

Last Updated

2025-03-24

Healthy Volunteers

Conditions

Acute Myeloid Leukaemia MDS (Myelodysplastic Syndrome)MPN (Myeloproliferative Neoplasms)

Interventions

DRUG

Monalizumab (anti-NKG2A monoclonal antibody)

Monalizumab (humZ270 mAb, IPH2201) is a humanized IgG4 monoclonal antibody targeting the NKG2A receptor on NK cells. Administered intravenously at a dose of 1 mg/kg on days +30 and +44 after haploidentical stem cell transplantation with post-transplant cyclophosphamide (PT-Cy) as GVHD prophylaxis, Monalizumab aims to enhance NK cell activity by blocking NKG2A. This intervention is unique in its timing, as it is given during a period when CD94/NKG2A+ NK cells are abundant, and its two-dose regimen is designed to optimize NK cell reconstitution. It targets patients with hematologic malignancies, such as AML and MDS, to improve GVHD-free and progression-free survival by enhancing NK cell-mediated immunity. This approach differs from other therapies by focusing on NK cell alloreactivity in the post-transplant setting. Cyclophosphamide is used as part of the pre-transplant conditioning regimen and is part of the inclusion criteria, but it is not part of the protocol-specific intervention.

Inclusion Criteria: 1. Patients capable of providing informed consent according to ICH/ GCP, and national/local regulations and be willing to comply with all study-related procedures. 2. Adult patients aged ≥18 years old, without any restriction of gender and race. 3. Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN). 4. Patients lacking a HLA identical donor and receiving haploidentical stem cell transplant with GVHD/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. 5. Patient who has received haplo-SCT with a myeloablative or reduced intensity or nonmyeloblative conditioning followed, either by a bone marrow or a peripheral blood stem cell (PBSC) graft. 6. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 8 days prior to start of study drug for women of childbearing potential. 7. 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: 1. Patients aged \< 18 years old. 2. Active uncontrolled infections. 3. CNS involvement of AML disease. 4. 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). 5. Pregnant or breast-feeding or intending to become pregnant during the study. 6. Patients who rapidly relapse after allogenic-SCT before day 30 after allogenic-SCT. 7. Patients who experience acute GVHD before day +30 after allogenic-SCT. 8. Patients treated with a second allogeneic Allo-SCT.

Locations (2)

IRCCS Ospedale Policlinico San Martino

Genova, GENOVA, Italy

Irccs Istituto Clinico Humanitas

Rozzano, MILANO, Italy