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
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
- 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.
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber Cancer Institute
-
-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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.
時間枠：Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
|
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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
時間枠：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
|
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.
時間枠：Immunological samples taken at study appointments during the 12 week protocol schedule
|
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
時間枠：Immunological samples taken at study appointments during the 12 week protocol schedule
|
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
|
協力者と研究者
協力者
協力者
捜査官
捜査官
- 主任研究者：John Koreth, MBBS, D.Phil、Dana-Farber Cancer Institute
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
研究開始
一次修了 (実際)
一次修了
研究の完了 (実際)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- 07-083
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