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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03977103
• Other study ID #: 02/14
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2014
• Est. completion date: February 28, 2023

Study information

• Verified date: January 2020
• Source: University Of Perugia
• Contact: Antonio Pierini, MD, PhD
• Phone: +390755784147
• Email: antonio.pierini[@]unipg.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 28, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Multiple Myeloma
• Myeloproliferative Disorders
• Other Hematologic Malignant Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• 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

Locations

Country	Name	City	State
Italy	University of Perugia	Perugia	PG

Sponsors (1)

Lead Sponsor	Collaborator
University Of Perugia

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	cumulative incidence of grades = 2 acute GvHD	cumulative incidence of grades = 2 acute GvHD according to NIH consesus criteria	6 months
Other	cumulative incidence of extensive chronic GvHD	cumulative incidence of extensive chronic GvHD according to revised NIH consesus criteria (Jagasia et al. BBMT 2015)	2 years
Other	cumulative incidence of non-relapse mortality	cumulative incidence of non-relapse mortality, defined as death by any cause in the absence of relapse, as competitive risk versus relapse	2 years
Other	cumulative incidence of relapse	cumulative incidence of relapse, defined as disease recurrence according to marrow morphology, flow cytometry, cytogenetics, fluorescence in situ hybridization and/or polymerase chain reaction, as competitive risk versus non-relapse mortality	2 years
Primary	chronic GvHD/relapse-free survival	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)	2 years
Secondary	full donor-type engraftment	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	30 days