Chronic Graft Versus Host DiseasePhase 1NCT01937468
Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
A Phase 1 study testing Treg-enriched infusion and Interleukin-2 in people with Chronic Graft Versus Host Disease and Chronic GVHD, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft Versus Host Disease, Chronic GVHD, Complications of Organ Transplant Stem Cells
- What is being tested?
- Treg-enriched infusion and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2013to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Recipient of allogeneic hematopoietic stem cell transplantation
- Participants must have steroid-refractory cGVHD. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D; section 17.4) 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. Participants with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible.
- Stable dose of glucocorticoids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
- Patient age 18 years old. Because no dosing or adverse event data are currently available on the use of IL-2 in participants <18 years of age, children are excluded from this study.
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- ECOG performance status 0-2 (Appendix A; section 17.1)
- Participants must have adequate organ function as defined below:
- Hepatic: Adequate hepatic function (total bilirubin <2.0 mg/dl-exception permitted in participants with Gilbert's Syndrome; AST (SGOT)/ALT (SGPT) ≤2x ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD. For participants with abnormal LFTs as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment. Abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation.
- Pulmonary: FEV1 ≥ 50% or DLCO(Hb) ≥ 40% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD
- Renal: Serum creatinine less than upper limit of normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Adequate bone marrow function indicated by ANC>1000/mm3 and platelets>50,000/mm3 without growth factors or transfusions
- Cardiac: No myocardial infarction within 6 months prior to enrollment or NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- The effects of IL-2 on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, 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
Who cannot join
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- 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 chronic GVHD therapies (e.g. gleevec, extracorporeal photopheresis, rituximab, immunosuppressive medications) in the 4 weeks prior
- Low-dose IL-2 therapy in the 4 weeks prior
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- Post-transplant exposure to T-cell or alternative 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
- Inability to comply with IL-2 treatment regimen
- 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 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 HSCT.
- Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator.
- Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Dana-Farber Cancer Insitute
Boston, Massachusetts, 02215
About this study
Official title: A Phase I Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. IL-2 is involved with cell signaling and regulation of white blood cells (WBCs). WBCs are part of the immune system. Treg cells are also part of the immune system; they are involved with anti-inflammatory responses. "Investigational" means that the combination of IL-2 and anti-inflammatory Treg cell infusion is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of IL-2 and anti-inflammatory Treg cell infusion for use in people with cGVHD.
Chronic GVHD is a medical condition that may occur after you have received your bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease.
Traditional standard therapy to treat cGVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigators are looking to assess the safety and optimal dose for the combination of IL-2 plus donor anti-inflammatory Treg cells, that may help control cGVHD by stopping the donor's immune system from 'rejecting' your body.
Read the detailed description
After the screening procedures confirm that you are eligible to participate in the research study: If you take part in this research study, you (and your donor) will have the following tests and procedures:
Donor Lymphocytes Collection: Lymphocytes are a type of white blood cell involved with the immune system. Your original marrow/stem cell donor will undergo one white blood cell collection procedures called leukapheresis. Blood from the vein in one arm will be circulated through a special machine to remove the white blood cells, and the rest of the blood will be returned to the donor's other arm. The cells collected from the leukapheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. A sample will be removed for study testing, and the remaining lymphocytes will be set-aside for infusion.
Donor Lymphocyte Processing: Once the lymphocytes are collected from your donor, the CliniMACS System device will enrich (preferentially select) the number of Treg cells. Samples will be taken before and after processing by the CliniMACS System to examine the cells. After completing the necessary safety tests, the Treg-enriched donor lymphocyte cells will be ready for administration.
Donor Cellular Infusion (DCI): The Treg-enriched donor lymphocytes will be infused through an intravenous (I.V.) catheter over approximately 5-10 minutes. Prior to the infusion, you will receive Tylenol and Benadryl to prevent transfusion related reactions. You will be observed for about 1 hour after the infusion. The total anticipated time you will spend in the clinic is approximately 2 hours.
Since the investigators are looking for the highest one-time dose of the anti-inflammatory donor cells that can be administered safely in combination with IL-2 without severe or unmanageable side effects in participants that have cGVHD, not everyone who participates in this research study will receive the same dose of the donor cells. The cell dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their cell doses.
Study Drug: You will give yourself or be given IL-2 daily through an injection under your skin. You will do this once every day for 8 weeks, starting from the day of donor Treg cell infusion. You will then have 4 weeks off of IL-2.
IL-2 will be provided in single-use (one-time only) syringes to be refrigerated at home at 36 - 46°F (2 - 8°C).
During the first 6 weeks of IL-2, you will continue to take steroids and other immune suppressing medications without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.
If your cGVHD improves after 8 weeks on IL-2, you may have the option of continuing extended-duration therapy. Extended-duration therapy is daily IL-2 treatment starting at the end-of-study visit after week 12. Your doctor will discuss this option with you. If you continue with extended-duration IL-2 therapy after completing the week 12 evaluation, you will be assessed on the following schedule:
- Clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks
- Immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.
Drug Diary: Each day for the first 8 weeks you take IL-2 and each day during extend-duration IL-2 (if applicable), you will be asked to document, in a drug diary, when you took the drug and where you injected it. The diary will also include special instructions for taking the study drug(s). The diary will also ask if the entire syringe was injected, and if there were other issues related to IL-2. You will be asked to return your drug diary to clinic every 14 days while you receive IL-2. If you continue taking IL-2 in the extend-duration portion, you will return your drug diary every 8 weeks (at your clinic visit).
Chronic GVHD Assessments: While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system (for example, whether you have experienced any nausea, vomiting, diarrhea, difficulty swallowing). The investigators will also look at the range of motion of different body parts (for example, your arms).
- Conditions
- Chronic Graft Versus Host Disease, Chronic GVHD, Complications of Organ Transplant Stem Cells
- Being tested
- Treg-enriched infusion, Interleukin-2
- Keywords
- Chronic GVHD, Chronic graft versus host disease, Allogeneic stem cell transplant
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treg-enriched infusionOther
Treg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema
Interleukin-2Drug
Also called IL-2
Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification).
| Study group | Role | What they receive |
|---|---|---|
| Treg-enriched infusion plus 8-week low-dose Interleukin-2 | Experimental | Treg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema. Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification). Receives: Other: Treg-enriched infusion; Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event profile and the maximum tolerate dose of Treg-enriched infusion plus 8-week low-dose IL-2
Adverse events are considered dose-limiting toxicities by the criteria defined in protocol Section 6.2. If 1 or 0 out of 5 participants in the same dose-level cohort experience a DLT, escalation to the next dose level will take place. If this is dose-level C, then dose C is the MTD. If 2 or more participants out of 5 in the same dose level experience a DLT, then the previous dose-level will be the MTD. If this is dose-level A, accrual will stop.
Measured: 24 weeks post Treg infusion, with continued follow-up for participants on extended duration IL-2 therapy.
Secondary outcomes (3)
To determine feasibility of Treg-enriched infusion plus 8-week low-dose IL-2
In the first 10 products, if 6 or fewer products meet release criteria the system will be considered infeasible and the study will be terminated early.
Measured: 2 Years
Clinical response of cGVHD as defined by the NIH consensus criteria to Treg-enriched infusion plus 8-week low-dose IL-2
The investigators will grade the participants' cGVHD per the NIH guidelines at baseline and after 8 weeks of low-dose IL-2 post Treg infusion. cGVHD response will be assessed according to NIH consensus criteria.
Measured: Baseline and 8 weeks post Treg infusion
Expansion of Treg cells in the peripheral blood after a Treg-enriched infusion plus 8-week low-dose IL-2
Peripheral blood samples will be taken at the various time points for immunological analysis including the measure of quantitative changes in individual immune cell populations, plasma levels of IL-2, and immunosuppressive ability of the expanded Treg cells.
Measured: Baseline, end of weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 of study paticipation. Also every 8 weeks for participants continuing on extended duration IL-2 therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2013 (estimated)
- Study startNov 2013
- Primary completionAug 2017
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH, Iovance Biotherapeutics, Inc., National Cancer Institute (NCI)
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS, DPhil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01937468
- Sponsor's protocol ID
- 13-281
- Other IDs
- R01CA183559-01
- Status last verified
- Feb 2026
- First submitted
- 30 Aug 2013
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Whangbo JS, Nikiforow S, Kim HT, Wahl J, Reynolds CG, Rai SC, Kim S, Burden A, Alho AC, Lacerda JF, Alyea EP, Cutler CS, Ho VT, Antin JH, Soiffer RJ, Ritz J, Koreth J. A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease. Blood Adv. 2022 Nov 8;6(21):5786-5796. doi: 10.1182/bloodadvances.2021006625.
PubMed 35475885
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
- ClinicalTrials.gov ID
- NCT01937468
- Acronym / sponsor ID
- 13-281
- Conditions
- Chronic Graft Versus Host Disease, Chronic GVHD, Complications of Organ Transplant Stem Cells
- Keywords
- Chronic GVHD, Chronic graft versus host disease, Allogeneic stem cell transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH, Iovance Biotherapeutics, Inc., National Cancer Institute (NCI)
- Study start
- Nov 2013
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 9 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. IL-2 is involved with cell signaling and regulation of white blood cells (WBCs). WBCs are part of the immune system. Treg cells are also part of the immune system; they are involved with anti-inflammatory responses. "Investigational" means that the combination of IL-2 and anti-inflammatory Treg cell infusion is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of IL-2 and anti-inflammatory Treg cell infusion for use in people with cGVHD.
Chronic GVHD is a medical condition that may occur after you have received your bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease.
Traditional standard therapy to treat cGVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigators are looking to assess the safety and optimal dose for the combination of IL-2 plus donor anti-inflammatory Treg cells, that may help control cGVHD by stopping the donor's immune system from 'rejecting' your body.
Detailed description
After the screening procedures confirm that you are eligible to participate in the research study: If you take part in this research study, you (and your donor) will have the following tests and procedures:
Donor Lymphocytes Collection: Lymphocytes are a type of white blood cell involved with the immune system. Your original marrow/stem cell donor will undergo one white blood cell collection procedures called leukapheresis. Blood from the vein in one arm will be circulated through a special machine to remove the white blood cells, and the rest of the blood will be returned to the donor's other arm. The cells collected from the leukapheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. A sample will be removed for study testing, and the remaining lymphocytes will be set-aside for infusion.
Donor Lymphocyte Processing: Once the lymphocytes are collected from your donor, the CliniMACS System device will enrich (preferentially select) the number of Treg cells. Samples will be taken before and after processing by the CliniMACS System to examine the cells. After completing the necessary safety tests, the Treg-enriched donor lymphocyte cells will be ready for administration.
Donor Cellular Infusion (DCI): The Treg-enriched donor lymphocytes will be infused through an intravenous (I.V.) catheter over approximately 5-10 minutes. Prior to the infusion, you will receive Tylenol and Benadryl to prevent transfusion related reactions. You will be observed for about 1 hour after the infusion. The total anticipated time you will spend in the clinic is approximately 2 hours.
Since the investigators are looking for the highest one-time dose of the anti-inflammatory donor cells that can be administered safely in combination with IL-2 without severe or unmanageable side effects in participants that have cGVHD, not everyone who participates in this research study will receive the same dose of the donor cells. The cell dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their cell doses.
Study Drug: You will give yourself or be given IL-2 daily through an injection under your skin. You will do this once every day for 8 weeks, starting from the day of donor Treg cell infusion. You will then have 4 weeks off of IL-2.
IL-2 will be provided in single-use (one-time only) syringes to be refrigerated at home at 36 - 46°F (2 - 8°C).
During the first 6 weeks of IL-2, you will continue to take steroids and other immune suppressing medications without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.
If your cGVHD improves after 8 weeks on IL-2, you may have the option of continuing extended-duration therapy. Extended-duration therapy is daily IL-2 treatment starting at the end-of-study visit after week 12. Your doctor will discuss this option with you. If you continue with extended-duration IL-2 therapy after completing the week 12 evaluation, you will be assessed on the following schedule:
- Clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks
- Immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.
Drug Diary: Each day for the first 8 weeks you take IL-2 and each day during extend-duration IL-2 (if applicable), you will be asked to document, in a drug diary, when you took the drug and where you injected it. The diary will also include special instructions for taking the study drug(s). The diary will also ask if the entire syringe was injected, and if there were other issues related to IL-2. You will be asked to return your drug diary to clinic every 14 days while you receive IL-2. If you continue taking IL-2 in the extend-duration portion, you will return your drug diary every 8 weeks (at your clinic visit).
Chronic GVHD Assessments: While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system (for example, whether you have experienced any nausea, vomiting, diarrhea, difficulty swallowing). The investigators will also look at the range of motion of different body parts (for example, your arms).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treg-enriched infusion plus 8-week low-dose Interleukin-2 | Experimental | Other: Treg-enriched infusion, Drug: Interleukin-2Treg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema. Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Recipient of allogeneic hematopoietic stem cell transplantation
- Participants must have steroid-refractory cGVHD. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D; section 17.4) 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. Participants with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible.
- Stable dose of glucocorticoids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
Key exclusion criteria (16 listed)
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- 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 chronic GVHD therapies (e.g. gleevec, extracorporeal photopheresis, rituximab, immunosuppressive medications) in the 4 weeks prior
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treg-enriched infusionTreg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema | Other | Treg-enriched infusion plus 8-week low-dose Interleukin-2 |
| Interleukin-2Also: IL-2Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification). | Drug | Treg-enriched infusion plus 8-week low-dose Interleukin-2 |
Primary outcome
Adverse event profile and the maximum tolerate dose of Treg-enriched infusion plus 8-week low-dose IL-2
Time frame: 24 weeks post Treg infusion, with continued follow-up for participants on extended duration IL-2 therapy.
Adverse events are considered dose-limiting toxicities by the criteria defined in protocol Section 6.2. If 1 or 0 out of 5 participants in the same dose-level cohort experience a DLT, escalation to the next dose level will take place. If this is dose-level C, then dose C is the MTD. If 2 or more participants out of 5 in the same dose level experience a DLT, then the previous dose-level will be the MTD. If this is dose-level A, accrual will stop.
3 secondary outcomes
To determine feasibility of Treg-enriched infusion plus 8-week low-dose IL-2
Time frame: 2 Years
Clinical response of cGVHD as defined by the NIH consensus criteria to Treg-enriched infusion plus 8-week low-dose IL-2
Time frame: Baseline and 8 weeks post Treg infusion
Expansion of Treg cells in the peripheral blood after a Treg-enriched infusion plus 8-week low-dose IL-2
Time frame: Baseline, end of weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 of study paticipation. Also every 8 weeks for participants continuing on extended duration IL-2 therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Derived from this study: PubMed 35475885Whangbo JS, Nikiforow S, Kim HT, Wahl J, Reynolds CG, Rai SC, Kim S, Burden A, Alho AC, Lacerda JF, Alyea EP, Cutler CS, Ho VT, Antin JH, Soiffer RJ, Ritz J, Koreth J. A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease. Blood Adv. 2022 Nov 8;6(21):5786-5796. doi: 10.1182/bloodadvances.2021006625.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Koreth, MBBS, DPhil principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treg-enriched infusion and Interleukin-2 in people with Chronic Graft Versus Host Disease and Chronic GVHD, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event profile and the maximum tolerate dose of Treg-enriched infusion plus 8-week low-dose IL-2 (time frame: 24 weeks post Treg infusion, with continued follow-up for participants on extended duration IL-2 therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01937468, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.