Acute Lymphoblastic Leukemia ALL, Acute Myeloid Leukaemia (AML), High Risk Leukaemia, Leukaemia Relapse
Conditions
Keywords
AML, ALL, SHARP, Total marrow/lymphoid irradiation, Treg, Tcon, Relapse
Brief summary
The study is a monocentric, interventional study that evaluates the efficacy of allogeneic HLA-matched or haploidentical transplantation consisting of an irradiation-based conditioning regimen coupled with donor Treg/Tcon adoptive immunotherapy for high-risk acute leukemia patients.
Interventions
RADIATIONtotal marrow/lymphoid irradiation
Combination of 20 Gy TMLI with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation
Sponsors
University Of Perugia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Simon's Minimax two-stage design has been chosen for predicting number of patients and duration of the study. Such design allows the investigator to early stop patient enrollment in case of unexpected futility.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* AML patients * Diagnosis of AML with indication to allogeneic hematopoietic cell transplantation. * Diagnosis of adverse genetic risk leukemia or presence of MRD or active disease (bone marrow infiltration 5-30%) at the time of the transplant procedure. * Availability of a hematopoietic stem cell donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years * ECOG ≤ 2 * HCT-CI ≤ 4 (51,52) * Absence of relevant psychiatric diseases * Signature of the informed consent ALL patients * Diagnosis of ALL, either T or B (Philadelphia negative) or mixed phenotype with indication to allogeneic transplant * Presence of MRD or active disease (bone marrow infiltration 5-30%) or patient with ≥ 2nd complete hematologic remission at the time of the transplant procedure. * Availability of a hematopoietic stem cell family donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years * ECOG ≤ 2 * HCT-CI ≤ 4 * Absence of relevant psychiatric diseases * Signature of the informed consent
Exclusion criteria
* AML patients * AML in CR MRD- * AML with \> 5% peripheral blasts or bone marrow infiltration ≥ 30% * Age \< 18 years or \> 65 years * ECOG \> 2 * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment * Pregnancy * No signature of the informed consent * ALL patients * ALL with \> 5% peripheral blasts or bone marrow infiltration ≥30% * Philadelphia positive ALL * Age \< 18 years or \> 65 years * ECOG \> 2 * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment * 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 irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy-based allogeneic transplantation from HLA-matched or haploidentical donors in high-risk acute leukemia 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 the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as full donor type engraftment. |
| Number of participants that developed grade ≥ 2 acute GvHD | 2 years | The study will also evaluate the impact of the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as 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 the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as chronic GvHD. |
Countries
Italy
Contacts
Primary ContactAntonio Pierini
Backup ContactLoredana Ruggeri
Outcome results
None listed