AML (Acute Myeloid Leukemia)
Conditions
Keywords
allogeneic stem cell transplantation, adoptive immunotherapy, Treg, high-risk AML
Brief summary
The study is a multicentric, interventional study that evaluates the efficacy of allogeneic HLA-matched allo-HSCT consisting of myeloablative conditioning coupled with donor Treg/Tcon adoptive immunotherapy for high-risk AML patients.
Interventions
BIOLOGICALHSCT with Treg/Tcon adoptive immunotherapy
Purified CD34+ hematopoietic progenitor cells with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation from HLA-matched related donor
Sponsors
Antonio Pierini
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is a multicentric, interventional study that evaluates the efficacy of allogeneic HLAmatched allo-HSCT consisting of myeloablative conditioning coupled with donor Treg/Tcon adoptive immunotherapy for high-risk AML patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AML with adverse genetic mutations in Complete Remission (CR) or incomplete (i) CR according to ELN 2022 recommendations with or without MRD positivity at the time of the HSCT procedure; * Diagnosis of AML with intermediate genetic mutations in Complete remission (CR) or incomplete (i) CR according to ELN 2022 with MRD positivity at the time of the transplant; * Fitness to undergo allo-HCT with myeloablative conditioning regimens according to center policy; * Availability of a family HLA-matched hematopoietic stem cell donor suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses. * Age ≥ 18 and ≤ 70 years * ECOG ≤ 2 * HCT-CI ≤ 4 * Signature of the informed consent
Exclusion criteria
* Prior allo-HSCT * AML with favorable genetic abnormalities * AML with intermediate genetic risk with MRD negativity * Active disease at transplant (\> 5% bone marrow infiltration) * Availability of a haploidentical or matched unrelated donor (MUD) * Age \< 18 years or \> 70 years * ECOG \> 2 * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment * Uncontrolled bacterial, viral, or fungal infections at time of enrollment * Pregnancy * No signature of the informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants free from disease 2 years after HSCT | 2 years | The primary objective of the study is to reduce the incidence of disease relapse after myeloablative conditioning regimen and Treg/Tcon adoptive immunotherapy-based allogeneic transplantation from HLA-matched donors in high-risk AML patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants that have reached engraftment 45 days after HSCT | 45 days | The study will also evaluate the impact of allo-HSCT from HLA-matched donors with myeloablative conditioning regimen and Treg/Tcon adoptive immunotherapy on full donor type engraftment |
| Number of participants that developed grade ≥ 2 acute GvHD | 100 days | The study will also evaluate the impact of allo-HSCT from HLA-matched donors with myeloablative conditioning regimen and Treg/Tcon adoptive immunotherapy on grade ≥ 2 acute GvHD |
| Number of participants free from chronic GvHD 2 years after HSCT | 2 years | The study will also evaluate the impact of allo-HSCT from HLA-matched donors with myeloablative conditioning regimen and Treg/Tcon adoptive immunotherapy on chronic GvHD |
| Number of participants who died for transplant related mortality after HSCT | 2 years | The study will also evaluate the impact of allo-HSCT from HLA-matched donors with myeloablative conditioning regimen and Treg/Tcon adoptive immunotherapy on non relapse mortality (NRM) |
| Number of patients free from ≥ 2 acute GvHD and/or moderate/severe chronic GvHD and/or relapse | 2 years | The study will also measure grade ≥ 2 acute GvHD and/or moderate/severe chronic GvHD/Relapse-free survival (GRFS) |
| Number of patients free from moderate/severe chronic GvHD and relapse | 2 years | The study will also measure moderate/severe chronic GvHD-Relapse-free survival (CRFS) |
| Number of patients alive after 2 years after allogeneic transplant | 2 years | Overall survival (OS) of patients treated with allogeneic transplant |
Countries
Italy
Contacts
CONTACTAntonio Pierini
PRINCIPAL_INVESTIGATORAntonio Pierini
University Of Perugia
Outcome results
None listed