Clinical trial NCT03977103: Irradiation-based Myeloablative Conditioning Followed by Treg/Tcon Immunotherapy in HSCT
Official title: Antileukemic Activity of Allogeneic Hematopoietic Stem Cell Transplantation With Fractionated Total Body Irradiation or Total Marrow and Lymph Node Irradiation Followed by Adoptive Immunotherapy With Regulatory and Conventional T Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Myeloproliferative Disorders
Lymphoma
Multiple Myeloma
Other Hematologic Malignant Neoplasms
Lead sponsor: University Of Perugia
Sponsor class: OTHER
First posted: 2019-06-06
Enrollment: 80
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate if hyper-fractionated TBI or TMLI followed by Treg/Tcon adoptive immunotherapy improve cGvHD/disease free survival after allogeneic HSCT in patients affected by high-risk acute leukemias or other hematologic malignancy where HSCT is indicated.

Detailed description: Improving cGvHD/disease free survival in patients with high-risk acute leukemias or other hematologic malignancy where HSCT is indicated with the use of a regulatory T cell based protocol. Hyper-fractionated Total Body Irradiation or Total Marrow and Lymphoid Irradiation based conditioning will be followed by the infusion of T regulatory and T conventional cell adoptive immunotherapy and a purified CD34+ hematopoietic stem cell graft. Incidence of Non Relapse Mortality, Relapse, acute Graft versus Host Disease, chronic Graft versus Host Disease, as well as probability of cGvHD/disease free survival will be assessed in patient subpopulations separated according to HLA-matching with the donor (HLA-matched HSCT and HLA-haploidentical HSCT) and type of disease (acute myeloid leukemia, acute lymphoid leukemia, lymphoma, multiple myeloma, myeloproliferative disease, and other).

Eligibility criteria: Inclusion Criteria:

* AML and ALL in complete remission and with high-risk of relapse
* AML and ALL primarily chemoresistant or relapsed;
* Chronic Myeloid Leukemia in accelerated or blastic phase;
* Patients affected by

  * Multiple myeloma,
  * Non Hodgkin lymphoma,
  * Hodgkin lymphoma,
  * Chronic myeloproliferative syndrome,
  * Chronic Lymphoid Leukemia,
  * Other Hematological malignancy at high-risk of relapse or detectable disease and where a HSCT is indicated.
* Age \<75 years
* ECOG ≤ 2
* Acceptable lung, liver, kidney, and heart function and absence of relevant psichiatric diseases
* Signature of the informed consent

Exclusion Criteria:

* Age \>75 years
* ECOG \> 2
* Not acceptable lung, liver, kidney, and heart function and presence of relevant psichiatric diseases
* Pregnancy
* No signature of the informed consent

Primary outcomes:
measure: chronic GvHD/relapse-free survival
timeFrame: 2 years
Secondary outcomes:
measure: full donor-type engraftment
timeFrame: 30 days
Other outcomes:
measure: cumulative incidence of grades ≥ 2 acute GvHD
timeFrame: 6 months
measure: cumulative incidence of extensive chronic GvHD
timeFrame: 2 years
measure: cumulative incidence of non-relapse mortality
timeFrame: 2 years
measure: cumulative incidence of relapse
timeFrame: 2 years
Locations:
city: Perugia
country: Italy
facility: University of Perugia
state: PG
Study officials:
affiliation: University Of Perugia
name: Andrea Velardi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011 Apr 7;117(14):3921-8. doi: 10.1182/blood-2010-10-311894. Epub 2011 Feb 3.
citation: Martelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, Pierini A, Massei MS, Amico L, Urbani E, Del Papa B, Zei T, Iacucci Ostini R, Cecchini D, Tognellini R, Reisner Y, Aversa F, Falini B, Velardi A. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014 Jul 24;124(4):638-44. doi: 10.1182/blood-2014-03-564401. Epub 2014 Jun 12.
citation: Pierini A, Ruggeri L, Carotti A, Falzetti F, Saldi S, Terenzi A, Zucchetti C, Ingrosso G, Zei T, Iacucci Ostini R, Piccinelli S, Bonato S, Tricarico S, Mancusi A, Ciardelli S, Limongello R, Merluzzi M, Di Ianni M, Tognellini R, Minelli O, Mecucci C, Martelli MP, Falini B, Martelli MF, Aristei C, Velardi A. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia. Blood Adv. 2021 Mar 9;5(5):1199-1208. doi: 10.1182/bloodadvances.2020003739.