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A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease (TREGeneration)

Primary Purpose

Graft vs Host Disease

Status

Unknown status

Phase

Phase 1

Locations

Portugal

Study Type

Interventional

Intervention

Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease

About this trial

This is an interventional treatment trial for Graft vs Host Disease focused on measuring Allogeneic hematopoietic stem cell transplantation, Graft vs host disease, Regulatory T cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs.
Stable immunosuppressive medication in the 4 weeks prior to initiation of treatment
PS 0-2 ECOG
Adequate liver, kidney, lung and hematopoietic system functions

Exclusion Criteria:

Pediatric patients
Pregnant women
Ongoing prednisone requirement >1 mg/kg/day (or equivalent)
Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)
New immunosuppressive medication in the 4 weeks prior
Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior
Exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior
Donor lymphocyte infusion within 100 days prior
Active malignant relapse
Active uncontrolled infection
HIV-infected patients

Sites / Locations

Instituto Portugues de OncologiaRecruiting
Hospital de Santa Maria, Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina MolecularRecruiting
Instituto Portugues de OncologiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Administration of 0.5 x 10ˆ6 donor Treg/kg

Administration of 1.0 x 10ˆ6 donor Treg/kg

Administration of 2.0-3.0 x 10ˆ6 donor Treg/kg

Administration of MTD of donor T reg

Arm Description

First group of 5 patients will receive a total of 0.5 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Second group of 5 patients will receive a total of 1.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Third group of 5 patients will receive a total of 2.0-3.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Preliminary Phase 2 study will include another 5 to 10 patients at the MTD identified in the Phase 1 study

Outcomes

Primary Outcome Measures

Progression of graft versus host disease according to the 2014 NIH consensus criteria and myelosuppression after the administration of 3 doses of donor regulatory T cells / kg recipient's body weight: 0.5 x 10ˆ6, 1.0 x 10ˆ6 and 2.0-3.0 x 10ˆ6 cells

Progression of graft versus host disease and myelosuppression are indicators of toxicity and MTD associated with the infusion of donor regulatory T cells

Secondary Outcome Measures

Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells

Total lymphocyte, CD4, CD8 and regulatory T cell counts after the infusion of donor regulatory T cells for the treatment of chronic graft versus host disease

Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease

Full Information

NCT ID

NCT02385019

First Posted

March 1, 2015

Last Updated

March 4, 2018

Sponsor

Instituto de Medicina Molecular João Lobo Antunes

Collaborators

Hospital de Santa Maria, Portugal, IPOFG Lisboa, Portugal, IPOFG Porto, Portugal

1. Study Identification

Unique Protocol Identification Number

NCT02385019

Brief Title

A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease

Acronym

TREGeneration

Official Title

A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Unknown status

Study Start Date

March 2015 (undefined)

Primary Completion Date

March 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Instituto de Medicina Molecular João Lobo Antunes

Collaborators

Hospital de Santa Maria, Portugal, IPOFG Lisboa, Portugal, IPOFG Porto, Portugal

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Phase 1/2 clinical study for the treatment of steroid-refractory chronic graft versus host disease after an allogeneic transplant of hematopoietic progenitors with donor CliniMACS-selected regulatory T cells

Detailed Description

Phase 1/2 clinical study evaluating safety (Phase 1) and preliminary efficacy (Phase 2) of donor regulatory T cells for patients with steroid-refractory chronic graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs. Phase 1 clinical trial will include groups of 5 patients sequentially treated with: 0.5 x 10ˆ6, 1.0 x 10ˆ6, 2-3 x 10ˆ6 donor Treg/kg. Phase 2 clinical trial will include another 5 to 10 patients treated with MTD. Donor Treg will be selected by the following sequential steps: - negative depletion of CD8 and CD19 cells - positive selection of CD25 cells

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft vs Host Disease

Keywords

Allogeneic hematopoietic stem cell transplantation, Graft vs host disease, Regulatory T cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Administration of 0.5 x 10ˆ6 donor Treg/kg

Arm Type

Experimental

Arm Description

First group of 5 patients will receive a total of 0.5 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Arm Title

Administration of 1.0 x 10ˆ6 donor Treg/kg

Arm Type

Experimental

Arm Description

Second group of 5 patients will receive a total of 1.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Arm Title

Administration of 2.0-3.0 x 10ˆ6 donor Treg/kg

Arm Type

Experimental

Arm Description

Third group of 5 patients will receive a total of 2.0-3.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.

Arm Title

Administration of MTD of donor T reg

Arm Type

Experimental

Arm Description

Preliminary Phase 2 study will include another 5 to 10 patients at the MTD identified in the Phase 1 study

Intervention Type

Biological

Intervention Name(s)

Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease

Intervention Description

Regulatory T cells selected by a sequential 2 step procedure: - Negative selection of CD8 and CD19 cells - Positive selection of CD25 cells

Primary Outcome Measure Information:

Title

Description

Progression of graft versus host disease and myelosuppression are indicators of toxicity and MTD associated with the infusion of donor regulatory T cells

Time Frame

Response evaluated 12 weeks after infusion

Secondary Outcome Measure Information:

Title

Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells

Time Frame

Response evaluated 12 weeks after infusion

Title

Total lymphocyte, CD4, CD8 and regulatory T cell counts after the infusion of donor regulatory T cells for the treatment of chronic graft versus host disease

Time Frame

Response evaluated 12 weeks after infusion

Title

Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease

Time Frame

Response evaluated 12 months after infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs. Stable immunosuppressive medication in the 4 weeks prior to initiation of treatment PS 0-2 ECOG Adequate liver, kidney, lung and hematopoietic system functions Exclusion Criteria: Pediatric patients Pregnant women Ongoing prednisone requirement >1 mg/kg/day (or equivalent) Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable) New immunosuppressive medication in the 4 weeks prior Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior Exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior Donor lymphocyte infusion within 100 days prior Active malignant relapse Active uncontrolled infection HIV-infected patients

Facility Information:

Facility Name

Instituto Portugues de Oncologia

City

Lisboa

ZIP/Postal Code

1099-023

Country

Portugal

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Isabelina Ferreira, MD

Phone

+351917502335

iferreira@ipolisboa.min-saude.pt

Facility Name

Hospital de Santa Maria, Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular

City

Lisboa

ZIP/Postal Code

1649-028

Country

Portugal

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joao F Lacerda, MD PhD

Phone

+351919727656

jlacerda@fm.ul.pt

Facility Name

Instituto Portugues de Oncologia

City

Porto

ZIP/Postal Code

4200-072

Country

Portugal

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carlos Pinho Vaz, MD

Phone

+351968014520

cpvaz@ipoporto.min-saude.pt

12. IPD Sharing Statement

Learn more about this trial

A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease

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