Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-host-Disease

NCT03683498 | Completed Phase 1 DMC

• 1 other identifier: GVHD-TReG
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib

Conditions

Chronic Graft vs Host Disease

Keywords

Ruxolitinib; T cells

Outcome Measures

Primary Outcomes (1)

• Toxicity and maximum tolerated dose

  To determine the maximum tolerated dose (MTD) and toxicity of Treg-enriched infusion among patients receiving ruxolitinib.

  Up 12 weeks after infusion

Secondary Outcomes (7)

• Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level.

  Before 24 hours to infusion up infusion day

• Clinical response of Treg-enriched infusion

  Up 12 weeks after Treg infusion

• Immunologic effects through phenotypical evaluation

  Up 12 weeks after Treg infusion

• Immunologic effects through immune globulins.

  Up 12 weeks after Treg infusion

• Immunologic effects through plasma banking

  Up 12 weeks after Treg infusion

Study Arms (1)

Regulatory T-cell enriched infusion

EXPERIMENTAL

Dose escalation sequential cohorts Regulatory T-cell enriched infusion (Cells/kg) will be administered. The cohorts will be dose escalated per the schema below: Dose-level A: 0.5 x 10ˆ6 Cells/kg Dose-level B: 1 x 10ˆ6 cell/kg Dose-level C: 2 x 10ˆ6 cell/kg

Biological: Regulatory T-cell enriched infusion

Interventions

Regulatory T-cell enriched infusion BIOLOGICAL

Enrichment of CD25hi regulatory T cells from CD8 and/or CD19 pre-depleted leukapheresis products.

Regulatory T-cell enriched infusion

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient of allogeneic hematopoietic stem cell transplantation.
• Participants must have steroid-refractory cGVHD and had obtained a partial response after at least 4 weeks of treatment with ruxolitinib.
• Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) despite the use of prednisone at ≥0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms.
• Stable dose of glucocorticoids for 4 weeks prior to enrolment
• No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
• No age limit. In the case of children participating in the study, the informed consent will be signed by a parents or legal guardians
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Participants must have adequate organ function
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Ongoing prednisone requirement \>1 mg/kg/day (or equivalent).
• Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
• History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
• New immunosuppressive medication in the 4 weeks prior.
• Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior.
• Post-transplant exposure to T-cell or Interleukin-2 targeted medication (e.g. alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
• Donor lymphocyte infusion within 100 days prior.
• Active malignant relapse.
• Active uncontrolled infection.
• Organ transplant (allograft) recipient.
• HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic hematopoietic stem cell transplant (HSCT). In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after hematopoietic stem cell transplant (HSCT).
• Other investigational drugs within 4 weeks prior to enrolment, unless cleared by the Principal Investigator.
• Pregnant women are excluded from this study.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead

Study Sites (1)

Hospital Universitario Virgen del Rocío

Seville, Seville, 41013, Spain

Location

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: 41637631 DERIVED

Study Officials

• José Antonio Pérez-Simón, M.D. Ph.D.

  Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Initial enrollment will be at Dose-level A. Subsequent cohorts will be dose escalated.

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 25, 2018
• Study Start: September 25, 2018
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: May 23, 2022

Record last verified: 2022-05

Locations

ES (1)