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Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-host-Disease (GVHD-TReG)

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ClinicalTrials.gov Identifier: NCT03683498
Recruitment Status : Active, not recruiting
First Posted : September 25, 2018
Last Update Posted : April 15, 2021
Sponsor:
Information provided by (Responsible Party):
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Study Description
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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

Condition or disease Intervention/treatment Phase
Chronic Graft vs Host Disease Biological: Regulatory T-cell enriched infusion Phase 1

Detailed Description:

The study design is based on a phase I trial in Spanish.

A number of 16 patients will be included to assess the safety and maximum tolerated dose-level of donor regulatory enriched T cell (Treg) in steroid-refractory chronic graft versus host disease (cGVHD) patients who did not obtain complete remission under treatment with ruxolitinib.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Initial enrollment will be at Dose-level A. Subsequent cohorts will be dose escalated.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 25, 2018
Estimated Primary Completion Date : March 22, 2022
Estimated Study Completion Date : March 22, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Regulatory T-cell enriched infusion

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


Outcome Measures
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Primary Outcome Measures :
  1. Toxicity and maximum tolerated dose [ Time Frame: Up 12 weeks after infusion ]
    To determine the maximum tolerated dose (MTD) and toxicity of Treg-enriched infusion among patients receiving ruxolitinib.


Secondary Outcome Measures :
  1. Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level. [ Time Frame: Before 24 hours to infusion up infusion day ]
    Percentage of cells viability, negative gram stain/endotoxin, percentage of CD4+CD25+ cells and CD4+CD25+CD127- Treg in order to consider for the infusion.

  2. Clinical response of Treg-enriched infusion [ Time Frame: Up 12 weeks after Treg infusion ]
    Each participant should be assigned one of the following categories: 1) complete cGVHD response per NIH criteria, 2) partial cGVHD response per NIH criteria, 3) non-response (includes stable disease) per NIH criteria, 4) progressive cGVHD per NIH criteria, 5) malignant disease relapse, or 6) unknown (not assessable, insufficient data).

  3. Immunologic effects through phenotypical evaluation [ Time Frame: Up 12 weeks after Treg infusion ]
    Phenotypical evaluation of T cell populations (CD4, CD8, Treg), B and NK cells nuclear cells of Treg-enriched infusion among patients receiving ruxolitinib.

  4. Immunologic effects through immune globulins. [ Time Frame: Up 12 weeks after Treg infusion ]
    Quantitative immune globulins of Treg-enriched infusion among patients receiving ruxolitinib

  5. Immunologic effects through plasma banking [ Time Frame: Up 12 weeks after Treg infusion ]
    Plasma banking of Treg-enriched infusion among patients receiving ruxolitinib

  6. Immunologic effects through additional mononuclear cells. [ Time Frame: Up 12 weeks after Treg infusion ]
    Storage of additional mononuclear cells of Treg-enriched infusion among patients receiving ruxolitinib

  7. Survival after one year of Treg infusion [ Time Frame: 1 year after Treg infusion ]
    Number of patients alive after one year of Treg infusion


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03683498


Locations
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Spain
Hospital Universitario Virgen del Rocío
Sevilla, Seville, Spain, 41013
Sponsors and Collaborators
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Investigators
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Principal Investigator: José Antonio Pérez-Simón, M.D. Ph.D. Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.
More Information
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Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
ClinicalTrials.gov Identifier: NCT03683498    
Other Study ID Numbers: GVHD-TReG
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: April 15, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:
Ruxolitinib
T cells
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases