NCT02385019

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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2015

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2015

Completed
Same day until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
10 days until next milestone

First Posted

Study publicly available on registry

March 11, 2015

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2019

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

March 6, 2018

Status Verified

March 1, 2018

Enrollment Period

4 years

First QC Date

March 1, 2015

Last Update Submit

March 4, 2018

Conditions

Graft vs Host Disease

Keywords

Allogeneic hematopoietic stem cell transplantationGraft vs host diseaseRegulatory T cells

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • 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

  • 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

  • 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

Study Arms (4)

Administration of 0.5 x 10ˆ6 donor Treg/kg

EXPERIMENTAL

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

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

Administration of 1.0 x 10ˆ6 donor Treg/kg

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

Administration of MTD of donor T reg

EXPERIMENTAL

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

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

Interventions

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

Regulatory T cells selected by a sequential 2 step procedure: 1. \- Negative selection of CD8 and CD19 cells 2. \- Positive selection of CD25 cells

Administration of 0.5 x 10ˆ6 donor Treg/kgAdministration of 1.0 x 10ˆ6 donor Treg/kgAdministration of 2.0-3.0 x 10ˆ6 donor Treg/kgAdministration of MTD of donor T reg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Instituto Portugues de Oncologia

Lisbon, 1099-023, Portugal

RECRUITING

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

Lisbon, 1649-028, Portugal

RECRUITING

Instituto Portugues de Oncologia

Porto, 4200-072, Portugal

RECRUITING

Related Publications (1)

  • Soares MV, Escamilla Gomez V, Azevedo RI, Pereira PNG, Caballero-Velazquez T, Mendes L, Alho AC, Garcia-Guerrero E, Garcia-Calderon CB, Tharmaratnam K, Cabral IA, Ribeiro AC, Juncal C, Roncon S, Pais AT, Rodriguez-Gil A, Espada ELDS, Rodrigues A, Garcao A, Yaspo ML, Warnatz HJ, Lehrach HR, Ward L, Barbosa-Morais NL, Quintas AM, Palmela P Sr, Caldas CMF, Ferreira R, Leite L, Martins C, Lourenco F, Moreno R, Campilho F, Cheyne CP, Garcia-Finana M, Campos AM, Baron F, Arpinati M, Hoffmann P, Edinger M, Koreth J, Ritz J, Pinho Vaz C, Perez-Simon JAA, Lacerda JF. Phase I/II Trials of Donor Regulatory T Cells for the Treatment of Steroid-Refractory Chronic Graft versus Host Disease. Blood Adv. 2026 Feb 4:bloodadvances.2025017996. doi: 10.1182/bloodadvances.2025017996. Online ahead of print.

    PMID: 41637631DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD, Associate Professor of Medicine

Study Record Dates

First Submitted

March 1, 2015

First Posted

March 11, 2015

Study Start

March 1, 2015

Primary Completion

March 1, 2019

Study Completion

December 1, 2019

Last Updated

March 6, 2018

Record last verified: 2018-03

Locations

PT(3)