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 posttransplantation cyclophosphamide.
- Conditions
- Patients with acute myeloid leukemia or myelodysplastic syndrome undergoing haploidentical transplantation with posttransplantation cyclophosphamide.MedDRA version: 21.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-005902-24-IT
- Lead Sponsor
- IRCCS ISTITUTO CLINICO HUMANITAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 42
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 and =70 years old, without any restriction of gender and race.
3) Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia or Myelodysplastic Syndrome (MDS).
4) Patients lacking a human leukocyte antigen (HLA) identical donor and receiving Haplo-SCT with GVHD/host versus graft (HVG) prophylaxis consisting of Cyclophosphamide: 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 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.
6) Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1) Patients aged < 18 or > 70 years old.
2) Active uncontrolled infections.
3) Central nervous system (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 Haplo-SCT.
7) Patients who experience acute GVHD before day +30 after Haplo-SCT.
8) Patients treated with a second allogeneic Allo-SCT.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the efficacy and safety of Monalizumab after Haplo-SCT with PT-Cy.;Secondary Objective: Evaluate the effect of monalizumab on the immunological reconstitution and other clinical parameters of survival and toxicity.;Primary end point(s): To evaluate the efficacy and safety of NKG2A blockade by Monalizumab after Haplo-SCT with PTCy in terms of GPFS.;Timepoint(s) of evaluation of this end point: 1 year.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Clinical Objectives: Evaluate the incidence of OS, PFS, NRM and post-transplant viral infections in patients receiving Monalizumab after Haplo-SCT.<br>Biological Objectives: Evaluate the reconstitution and alloreactive functions of NK cell population against leukemic cells after Monalizumab administration.;Timepoint(s) of evaluation of this end point: 1 year.