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

Graft vs Host Disease Clinical Trial

— TREGeneration  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02385019
• Other study ID #: TREGeneration-Portugal
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 1, 2015
• Last updated: March 4, 2018
• Start date: March 2015
• Est. completion date: December 2019

Study information

• Verified date: March 2018
• Source: Instituto de Medicina Molecular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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:

1. - negative depletion of CD8 and CD19 cells

2. - positive selection of CD25 cells

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: December 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Stable immunosuppressive medication in the 4 weeks prior to initiation of treatment

3. PS 0-2 ECOG

4. Adequate liver, kidney, lung and hematopoietic system functions

Exclusion Criteria:

1. Pediatric patients

2. Pregnant women

3. Ongoing prednisone requirement >1 mg/kg/day (or equivalent)

4. Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)

5. New immunosuppressive medication in the 4 weeks prior

6. Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior

7. Exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior

8. Donor lymphocyte infusion within 100 days prior

9. Active malignant relapse

10. Active uncontrolled infection

11. HIV-infected patients

Related Conditions & MeSH terms

• Graft vs Host Disease

Intervention

Biological:
• Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease
Regulatory T cells selected by a sequential 2 step procedure: - Negative selection of CD8 and CD19 cells - Positive selection of CD25 cells

Locations

Country	Name	City	State
Portugal	Hospital de Santa Maria, Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular	Lisboa
Portugal	Instituto Portugues de Oncologia	Lisboa
Portugal	Instituto Portugues de Oncologia	Porto

Sponsors (4)

Lead Sponsor	Collaborator
Instituto de Medicina Molecular	Hospital de Santa Maria, Portugal, IPOFG Lisboa, Portugal, IPOFG Porto, Portugal

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Response evaluated 12 weeks after infusion
Secondary	Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells		Response evaluated 12 weeks after infusion
Secondary	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		Response evaluated 12 weeks after infusion
Secondary	Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease		Response evaluated 12 months after infusion