Anti-NKG2A Monoclonal Antibody for AML or MDS Patients Undergoing Haploidentical Transplantation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorIstituto Clinico Humanitas
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Single group
Treatments tested in this trial
Monalizumab (anti-NKG2A monoclonal antibody)
DrugMonalizumab (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.
Treatment groups
42 Participants
are divided into 1 treatment groupGroup A: monalizumab treatment armExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
GPFS will be evaluated 1 year after Haplo-SCT with PT-Cy and Monalizumab administration on day +30 and +44.Secondary outcomes
1
Overall Survival (OS)
Overall Survival (OS) is defined as the time from Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) and Monalizumab administration until death from any cause. It is a key indicator of the overall benefit of the treatment, evaluating whether the addition of Monalizumab improves long-term survival in patients undergoing Haplo-SCT.
Time frame
Overall Survival (OS) will be evaluated at 1 year after Haplo-SCT2
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) and Monalizumab administration until the occurrence of disease progression or relapse. PFS evaluates the efficacy of Monalizumab in delaying or preventing the progression of hematological malignancies, such as Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), after Haplo-SCT.
Time frame
PFS will be evaluated at 1 year after Haplo-SCT3
Non-Relapse Mortality (NRM)
Non-Relapse Mortality (NRM) refers to mortality from causes other than disease relapse or progression, such as complications due to GVHD, infections, or other treatment-related toxicities. NRM will evaluate whether Monalizumab affects the risk of death from non-disease related causes in patients post-Haplo-SCT.
Time frame
NRM will be evaluated at 1 year after Haplo-SCT4
Incidence of Acute and Chronic GVHD
This measure tracks the incidence of acute and chronic GVHD in patients after Haplo-SCT with PT-Cy and Monalizumab treatment. It evaluates whether the addition of Monalizumab affects the rate of GVHD development.
Time frame
GVHD incidence will be assessed at 6 months and 1 year after Haplo-SCTSponsors and contacts
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Source ClinicalTrials.gov