Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft Versus Host Disease
A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease
A tanulmány áttekintése
Részletes leírás
- 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.
- Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 1. fázis
Kapcsolatok és helyek
Tanulmányi helyek
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Massachusetts
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Boston, Massachusetts, Egyesült Államok, 02115
- Dana-Farber Cancer Institute
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion Criteria:
- Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
- Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
- Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months without complete resolution of signs and symptoms.
- Stable dose of corticosteroids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment.
- Adequate bone marrow, renal and hepatic function as outlined in the protocol
- 18 years of age or older
- ECOG Performance Status of 0-2
Exclusion Criteria:
- Ongoing prednisone requirement > 1mg/kg/day (or equivalent)
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
- Concurrent ECP therapy within 4 weeks prior to enrollment
- Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
- Donor lymphocyte infusion within 100 days prior to IL-2 therapy
- Active malignant disease relapse
- Active, uncontrolled infection
- Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
- HIV seropositivity
- Life expectancy < 3 months
- Pregnancy or lactation
- Inability to comply with IL-2 treatment regimen
- Uncontrolled cardiac angina or symptomatic congestive heart failure
- Organ transplant (allograft) recipient
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
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Kísérleti: Interleukin-2
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) |
Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks.
Más nevek:
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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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.
Időkeret: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
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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. |
Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
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The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
Időkeret: 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
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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 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
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CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
Időkeret: Immunological samples taken at study appointments during the 12 week protocol schedule
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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). |
Immunological samples taken at study appointments during the 12 week protocol schedule
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Treg Cell:Tcon Cell Ratio
Időkeret: Immunological samples taken at study appointments during the 12 week protocol schedule
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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). |
Immunological samples taken at study appointments during the 12 week protocol schedule
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Együttműködők és nyomozók
Szponzor
Nyomozók
- Kutatásvezető: John Koreth, MBBS, D.Phil, Dana-Farber Cancer Institute
Publikációk és hasznos linkek
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Becslés)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- 07-083
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