A Phase 1 interventional study of Interleukin-2 in Graft Versus Host Disease, sponsored by Dana-Farber Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-01.
Sponsored by Dana-Farber Cancer Institute · Phase 1, Interventional, and Treatment
The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.
376 studies on the registry are indexed under Bronchiolitis Obliterans Syndrome; 104 are open to participants now.
This study's enrollment of 29 is below the median of 35 across 296 interventional studies indexed under Bronchiolitis Obliterans Syndrome.
Browse Bronchiolitis Obliterans Syndrome studies →Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.
Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels: Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d)
Drug: Interleukin-2
Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks.
Also known as: IL-2
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
Three dose levels were evaluated to determine the maximally tolerated dose (MTD): Dose level A: 0.3 x 10\^6 IU/m\^2/day Dose level B: 1.0 x 10\^6 IU/m\^2/day Dose level C: 3.0 x 10\^6 IU/m\^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
Time frame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
Feasibility: the number of participants who tolerated at least 6 weeks of therapy, and were thus evaluable for response. Efficacy: chronic GVHD response per NIH consensus criteria in evaluable patients. A complete response was defined as resolution of all reversible chronic GVHD-associated manifestations, a partial response as an improvement of 50% or more on the organ-specific chronic GVHD scale without progression at other organs or sites, progressive disease as an increase of 25% or more on the organ specific chronic GVHD scale, and stable disease as an improvement of less than 50% or increase of less than 25%. Please refer to the Supplementary Appendix in our published report (Koreth et al, NEJM 2011) for further details.
Time frame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12
CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
Changes in the above immune cell populations (CD3+T, CD4+T (including CD4+Treg and CD4+Tcon), CD8+T, NK, NKT and B cell counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy. All study participants (n=28) with a sample available were reported in the data table. Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Time frame: Immunological samples taken at study appointments during the 12 week protocol schedule
Treg Cell:Tcon Cell Ratio
Changes in the ratio of the CD4+ regulatory T cell (Treg) and CD4+ conventional T cell (Tcon) counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy. All study participants (n=28) with a sample available were reported in the data table. Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Time frame: Immunological samples taken at study appointments during the 12 week protocol schedule
| Milestone | Ultra-low Dose Interleukin-2 |
|---|---|
| Started | 29 |
| Completed | 28 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
Three dose levels were evaluated to determine the maximally tolerated dose (MTD): Dose level A: 0.3 x 10\^6 IU/m\^2/day Dose level B: 1.0 x 10\^6 IU/m\^2/day Dose level C: 3.0 x 10\^6 IU/m\^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
| million IU/m2/day | Ultra-low Dose IL-2 MTD |
|---|---|
| The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids. | 1 |
Feasibility: the number of participants who tolerated at least 6 weeks of therapy, and were thus evaluable for response. Efficacy: chronic GVHD response per NIH consensus criteria in evaluable patients. A complete response was defined as resolution of all reversible chronic GVHD-associated manifestations, a partial response as an improvement of 50% or more on the organ-specific chronic GVHD scale without progression at other organs or sites, progressive disease as an increase of 25% or more on the organ specific chronic GVHD scale, and stable disease as an improvement of less than 50% or increase of less than 25%. Please refer to the Supplementary Appendix in our published report (Koreth et al, NEJM 2011) for further details.
| participants | Ultra-low Dose Interleukin-2 |
|---|---|
| Feasibility | 23 |
| Efficacy | 12 |
Changes in the above immune cell populations (CD3+T, CD4+T (including CD4+Treg and CD4+Tcon), CD8+T, NK, NKT and B cell counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy. All study participants (n=28) with a sample available were reported in the data table. Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
| cells/cubic millimeter | Median Absolute Cell Counts at Baseline | Median Absolute Cell Counts at Week 8 | Median Absolute Cell Count at Week 12 |
|---|---|---|---|
| Treg cell count | 17 (6 to 35) | 101 (43 to 236) | 32 (11 to 92) |
| Tcon cell count | 206 (131 to 412) | 270 (110 to 678) | 209 (153 to 550) |
| CD8+ T cell count | 210 (113 to 419) | 202 (74 to 418) | 187 (55 to 502) |
| Natural Killer (NK) cell count | 158 (94 to 250) | 362 (170 to 570) | 203 (132 to 311) |
| NKT cell count | 28 (10 to 46) | 31 (18 to 53) | 22 (10 to 38) |
Changes in the ratio of the CD4+ regulatory T cell (Treg) and CD4+ conventional T cell (Tcon) counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy. All study participants (n=28) with a sample available were reported in the data table. Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
| ratio | Median Treg:Tcon Ratio at Baseline | Median Treg:Tcon Ratio at Week 8 | Median Treg:Tcon Ratio at Week 12 |
|---|---|---|---|
| Treg Cell:Tcon Cell Ratio | 0.07 (0.05 to 0.12) | 0.4 (0.24 to 0.71) | 0.14 (0.09 to 0.22) |
Collected over 12 weeks. For patients who continued on extended-duration therapy, adverse events were reported as long as they received treatment.. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ultra-low Dose Interleukin-2 | — | 9/29 (31%) | 4/29 (13.8%) |
| Event | Ultra-low Dose Interleukin-2 |
|---|---|
| Thrombotic microangiopathy with renal failureBlood and lymphatic system disorders | 2/29 |
| Acute myocardial infarctionCardiac disorders | 2/29 |
| Injection site indurationGeneral disorders | 2/29 |
| MRSA PneumoniaInfections and infestations | 1/29 |
| MRSA furuncleInfections and infestations | 1/29 |
| Hemophilius influenza type B bacteremiaInfections and infestations | 1/29 |
| Event | Ultra-low Dose Interleukin-2 |
|---|---|
| Constitutional symptomsGeneral disorders | 2/29 |
| Renal dysfunction (mild)Renal and urinary disorders | 1/29 |
| Thrombocytopenia (mild)Blood and lymphatic system disorders | 1/29 |
| Age, Categorical(Participants) | Group 1 |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 29 |
| >=65 years | 0 |
| Age, Continuous(years) | Group 1 |
|---|---|
| Mean | 46.5 ± 12.7 |
| Sex: Female, Male(Participants) | Group 1 |
|---|---|
| Female | 8 |
| Male | 21 |
| Region of Enrollment(participants) | Group 1 |
|---|---|
| United States | 29 |
This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
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Bronchiolitis Obliterans Syndrome→
Dana-Farber Cancer Institute