Clinical trial NCT06845592: Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia
Official title: SHARP - Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Myeloid Leukaemia (AML)
Acute Lymphoblastic Leukemia ALL
High Risk Leukaemia
Leukaemia Relapse
Keywords: AML
ALL
SHARP
Total marrow/lymphoid irradiation
Treg
Tcon
Relapse
Lead sponsor: University Of Perugia
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants free from disease 2 years after HSCT
timeFrame: 2 years
Secondary outcomes:
measure: Number of participants that have reached engraftment 45 days after HSCT
timeFrame: 45 days
measure: Number of participants that developed grade ≥ 2 acute GvHD
timeFrame: 2 years
measure: Number of participants free from chronic GvHD 2 years after HSCT
timeFrame: 2 years
Other outcomes:
Locations:
city: Perugia
country: Italy
facility: Università degli Studi di Perugia
state: PG
Study officials:
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