Irradiation-based Myeloablative Conditioning Followed by Treg/Tcon Immunotherapy in HSCT

Phase 2

• Conditions: Other Hematologic Malignant Neoplasms; Myeloproliferative Disorders; Acute Myeloid Leukemia; Multiple Myeloma; Acute Lymphoid Leukemia; Lymphoma
• Interventions: Biological: High dose irradiation conditioning + Treg/Tcon

• Registration Number: NCT03977103
• Lead Sponsor: University Of Perugia

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).

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2019-06-04
• Study First Submitted QC: 2019-06-04
• Study First Posted: 2019-06-06
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-08
• Last Update Posted: 2020-01-13
• Primary Completion: 2023-02-28
• Study Completion: 2023-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High dose irradiation conditioning + Treg/Tcon	High dose irradiation conditioning + Treg/Tcon	High dose irradiation based conditioning regimens followed by infusion of donor regulatory and conventional T cells and purified CD34+ hematopoietic stem cell transplantation

Primary Outcome Measures

Name	Time	Method
chronic GvHD/relapse-free survival	2 years	To evaluate if irradiation based myeloablative conditioning followed by Treg/Tcon adoptive immunotherapy improve chronic GvHD/relapse-free survival (GRFS) after allogeneic HSCT in patients affected by acute leukemias or other hematologic malignancies where HSCT is indicated. GRFS will be assessed in subgroups of patients separated according to HLA-matching with the donor and type of disease (acute myeloid lekemia, acute lymphoid leukemia, other)

Secondary Outcome Measures

Name	Time	Method
full donor-type engraftment	30 days	neutrophil and platelet engraftment measured by neutrophil counts \>500/mmc for 3 consecutive days and platelets count \>20000/mmc with 7 consecutive without platelet transfusion

Trial Locations

Locations (1)

University of Perugia; 🇮🇹 Perugia, PG, Italy