Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease
A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease
RATIONALE: Pentostatin may be effective in treating chronic graft-versus-host disease by stopping the immune system from rejecting donor stem cells or donor white blood cells.
PURPOSE: This phase II trial is studying how well pentostatin works in treating patients with chronic graft-versus-host disease that is refractory (not responsive) to treatment with steroids.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the response rate in patients with refractory chronic graft-versus-host disease treated with pentostatin.
Secondary
- Determine the time to next immunosuppressive agent (i.e., the time to progression from best response) in patients treated with this drug.
- Determine the toxicity of this drug in these patients.
- Determine the infection rate in patients treated with this drug.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the changes in lymphocyte populations in patients treated with this drug.
- Determine the survival of patients treated with this drug.
OUTLINE: This is a multicenter study.
Patients receive pentostatin IV over 20-30 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients who achieve a complete response after 6 courses receive 4 additional courses. Patients who achieve a partial response, minor response, or stable disease after 6 courses may receive up to 6 additional courses.
Patients are followed every 4 weeks for 1 year, every 3 months for 2 years, and then annually for 5 years.
PROJECTED ACCRUAL: Approximately 37 patients will be accrued for this study.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Delaware
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Lewes、Delaware、アメリカ、19958
- Tunnell Cancer Center at Beebe Medical Center
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Newark、Delaware、アメリカ、19713
- CCOP - Christiana Care Health Services
-
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Illinois
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Chicago、Illinois、アメリカ、60637-1470
- University of Chicago Cancer Research Center
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Chicago、Illinois、アメリカ、60612-7243
- University of Illinois Cancer Center
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Maryland
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Baltimore、Maryland、アメリカ、21201
- Greenebaum Cancer Center at University of Maryland Medical Center
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Elkton、Maryland、アメリカ、21921
- Union Hospital Cancer Program at Union Hospital
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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic Cancer Center
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New Jersey
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Voorhees、New Jersey、アメリカ、08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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New York、New York、アメリカ、10021
- New York Weill Cornell Cancer Center at Cornell University
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke Comprehensive Cancer Center
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Winston-Salem、North Carolina、アメリカ、27157-1096
- Wake Forest University Comprehensive Cancer Center
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Ohio
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Columbus、Ohio、アメリカ、43210-1240
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19111-2497
- Fox Chase Cancer Center - Philadelphia
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Philadelphia、Pennsylvania、アメリカ、19104-4283
- Abramson Cancer Center of the University of Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15224-1791
- Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
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Virginia
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Richmond、Virginia、アメリカ、23298-0037
- Virginia Commonwealth University Massey Cancer Center
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参加基準
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
- Histologic documentation of chronic GvHD following allogeneic HCT or donor lymphocyte infusion.
- Patients may have progressive, quiescent, or de novo onset chronic GvHD.
Patients with extensive stage chronic GvHD requiring systemic immunosuppressive therapy are eligible. Patients with limited stage disease are excluded. Extensive stage is defined according to Seattle criteria (9) as either:
- Generalized skin involvement or
Limited skin involvement or hepatic involvement with any one of the following:
- Liver histology showing chronic progressive hepatitis, bridging necrosis or cirrhosis
- Eye involvement (Schirmer's test with < 5 mm wetting)
- Involvement of minor salivary glands or oral mucosa
- Involvement of any other organ
Patients must have failed treatment with, or experience progression after, prior corticosteroids for extensive stage chronic GvHD, as defined below.
4.1 Patients will be considered to have failed corticosteroids if they have any one of the following criteria:
- Progressive disease or less than a minor response in any organ system despite 2 weeks on corticosteroid treatment at least 1 mg/kg methylprednisolone or equivalent.
- Failure to achieve at least a minor response after at least 4 weeks of treatment with a dose of ≥ 0.5 mg/kg methylprednisolone or equivalent.
- Achievement of less than a partial response at 8 weeks of corticosteroid treatment despite use of a dose ≥ 0.5 mg/kg methylprednisolone or equivalent.
- Requirement of ≥ 0.5 mg/kg methylprednisolone or equivalent to maintain a partial response or better at 12 weeks of corticosteroid treatment.
- Requirement of > 10 mg/kg methylprednisolone or equivalent to maintain a partial response or better at 18 weeks of corticosteroid treatment.
4.2 Patients with progression of extensive stage chronic GvHD after a prior history of treatment with at least 18 weeks of corticosteroids, now requiring the reintroduction of corticosteroids (> 10 mg/day methylprednisolone or equivalent) or an additional agent (including photopheresis, PUVA) for treatment.
- Patients with established chronic GvHD not improving or progressing on other immunosuppressive agents are also eligible if steroid refractoriness has been established previously.
- Age ≥ 18 years
- Performance Status 0-3
- Patients on mechanical ventilation are excluded.
- No active infection. Patients with active infection requiring antibiotic therapy are not eligible until infection is controlled.
- No HIV infection. Patients with HIV infection are excluded because of safety concerns in this patient population.
- Non-pregnant and non-nursing. Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial (although it is unlikely that successful pregnancy will occur in patients with chronic GvHD). Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).
Required Initial Laboratory Values:
- Calc. Creatinine Clearance ≥ 30 mL/min/1.73 m^2
- ANC > 1000/μL
- Platelets > 50,000/μL without transfusion
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：支持療法
- 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）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Pentostatin
treatment of pts with refractory graft vs host disease
|
4 mg/sq m IV infusion over 20-30 min q 2 weeks
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Response Rate
時間枠：3 months
|
Percentage of participants who had a complete or partial response defined by the Hopkins scoring system. A complete response is defined as the disappearance of signs and symptoms of chronic GVHD in all involved systems that is sustained for at lest 4 weeks. A partial response is an improvement by 2 or more points in at least one system score, which is sustained for at least 4 weeks, with no signs of worsening in others. |
3 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Grade 3 or Higher Non-hematologic Adverse Events
時間枠：Duration of treatment (up to 5 years)
|
Number of participants experiencing a grade 3, 4 or 5 clinically significant non-hematologic adverse events, at least possibly related to treatment.
|
Duration of treatment (up to 5 years)
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Overall Survival At 1 Year
時間枠：1 year
|
Percentage of patients who were alive at 1 year.
|
1 year
|
|
Overall Survival At 2 Years
時間枠：2 year
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Percentage of patients who were alive at 2 years.
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2 year
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Pharmacokinetics Association Between Exposure and Response At 3 Months
時間枠：3 months
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The individual PK parameters will be derived by using a noncompartmental analysis of the plasma-concentration-time data
|
3 months
|
協力者と研究者
捜査官
- スタディチェア：Sherif S. Farag, MD, PhD、Ohio State University
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
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
詳しくは
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