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

NCT06892223 | Recruiting Phase 2

• 3 other identifiers: ONC-2020-0012024-516974-31-002020-005902-24
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

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

Keywords

MONALIZUMAB; ALLOGENIC TRANSPLANT; ACUTE MYELOID LEUKEMIA; MYELODYSPLASTIC SYNDROM; MYELOPROLIFERATIVE NEOPLASM; GVHD

Outcome Measures

Primary Outcomes (1)

• Graft-versus-host disease-free and progression-free survival (GPFS)

  GPFS is defined as the time from Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) until the occurrence of either graft-versus-host disease (GVHD) or disease progression/relapse. This measure evaluates the combined effect of Monalizumab (NKG2A blockade) in preventing both GVHD and disease progression. It is a comprehensive indicator of treatment efficacy, assessing whether the addition of Monalizumab improves patient outcomes by prolonging the period free of both GVHD and disease progression.

  GPFS will be evaluated 1 year after Haplo-SCT with PT-Cy and Monalizumab administration on day +30 and +44.

Secondary Outcomes (5)

• Overall Survival (OS)

  Overall Survival (OS) will be evaluated at 1 year after Haplo-SCT

• Progression-Free Survival (PFS)

  PFS will be evaluated at 1 year after Haplo-SCT

• Non-Relapse Mortality (NRM)

  NRM will be evaluated at 1 year after Haplo-SCT

• Incidence of Acute and Chronic GVHD

  GVHD incidence will be assessed at 6 months and 1 year after Haplo-SCT

• Post-transplant Viral Infections

  Post-transplant viral infections will be assessed until 100 days after Haplo-SCT

Study Arms (1)

monalizumab treatment arm

EXPERIMENTAL

This study includes a single arm, where all patients will receive Monalizumab (humZ270 mAb, IPH2201), an anti-NKG2A monoclonal antibody, as the intervention. Monalizumab is administered intravenously at a dose of 1 mg/kg on day +30 and day +44 after undergoing haploidentical stem cell transplantation (Haplo-SCT). The use of post-transplantation cyclophosphamide (PT-Cy) is part of the conditioning regimen and inclusion criteria but is not part of the protocol-specified intervention. Monalizumab aims to enhance the immune function of NK cells by blocking the NKG2A receptor, potentially improving graft-versus-host disease (GVHD)-free and progression-free survival (GPFS).

Drug: Monalizumab (anti-NKG2A monoclonal antibody)

Interventions

Monalizumab (anti-NKG2A monoclonal antibody) DRUG

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.

Also known as: humZ270, mAb IPH2201

monalizumab treatment arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 years old, without any restriction of gender and race.
• Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN).
• 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.
• 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.
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 8 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.

You may not qualify if:

• Patients aged \< 18 years old.
• Active uncontrolled infections.
• 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 allogenic-SCT.
• Patients who experience acute GVHD before day +30 after allogenic-SCT.
• Patients treated with a second allogeneic Allo-SCT.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (2)

IRCCS Ospedale Policlinico San Martino

Genova, GENOVA, 16132, Italy

RECRUITING

Irccs Istituto Clinico Humanitas

Rozzano, MILANO, 20089, Italy

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Myeloproliferative Disorders

Interventions

monalizumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Central Study Contacts

DOMENICO MAVILIO, MD

CONTACT

+39 02 8224 5157; domenico.mavilio@humanitas.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: March 24, 2025
• Study Start: December 3, 2021
• Primary Completion: March 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)