STI571 ProspectIve RandomIzed Trial: SPIRIT (SPIRIT)
A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic Myelogenous Leukemia (CML) in Chronic Phase
To test whether increasing the dose of imatinib or combining it with IFNalpha or ara-C increases the rate of molecular response (as measured by the decrease in BCR-ABL transcripts after 12 months of treatment) in patients with previously untreated CML in chronic phase.
To compare overall survival in a selected arm according to molecular response at 1 year from randomization with the reference arm.
調査の概要
状態
条件
詳細な説明
Imatinib at 400 mg daily has emerged as the preferred therapy for newly diagnosed CML patients who do not undergo allogeneic stem cell transplant.
A phase III randomized study, comparing imatinib at 400 mg per day to interferon plus cytarabine in newly diagnosed chronic phase CML patients enrolled 1106 patients from June 2000 to January 2001. 553 patients were randomized to each treatment. For comparative purposes, at 6 months, 75% of patients randomized to imatinib obtained a major cytogenetic response with 51% complete responses. Despite these impressive results, only a minority of patients treated with imatinib in this study achieved a molecular remission. When analyzed by log reduction in Bcr-Abl transcript levels using quantitative RT-PCR, 39% of patients achieved a 3-log reduction in Bcr-Abl levels, but only 13% and 3% achieved a 4- and 5-log reduction, respectively.2 To improve upon these results, various groups have tried higher doses of imatinib, and combinations of imatinib with interferon alpha or cytarabine. Each of these studies has used cytogenetic responses as the major endpoint.
Each of these therapies has increased toxicity as compared to 400 mg of imatinib alone and the rates of molecular remissions have not been reported.
Thus the purpose of this study is to first determine whether higher doses of imatinib or combining Imatinib with interferon or Ara-C would result in higher rates of molecular responses and if so, in better survival.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Poitiers、フランス、86021
- University Hospital
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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
Inclusion Criteria:
- Patients over 18 years of age
- Patients with Bcr-Abl positive CML in chronic phase.
- Patients within 14 weeks of diagnosis and previously untreated for CML except for hydroxyurea and/or anagrelide.
- No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- ECOG performance score of 0-2
- acceptable hepatic, renal, and cardiac function
- Informed consent signed up
Exclusion Criteria:
- Depressive syndrome not controlled
- Uncontrolled medical illnesses.
- Women with childbearing potential and male patients who are unwilling or unable to use an adequate method to avoid pregancy for the entire period of the study
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:ランダム化
- 介入モデル:並列代入
- 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 |
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実験的:Imatinib mesylate 400 mg
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実験的:Imatinib mesylate 600 mg
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実験的:Imatinib mesylate 400 mg +Peg interferon
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実験的:Imatinib mesylate 400 mg +Cytarabine
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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
結果測定 |
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Overall survival improvement
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二次結果の測定
結果測定 |
時間枠 |
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Molecular response improvement at 1 year
時間枠:1 year
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1 year
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Hematological, cytogenetic responses improvement
時間枠:1 year
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1 year
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Duration of responses improvement
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Survival without progression improvement
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Acceptable toxicity
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協力者と研究者
捜査官
- スタディチェア:François GUILHOT, MD、Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE
出版物と役立つリンク
一般刊行物
- Bruzzoni-Giovanelli H, Gonzalez JR, Sigaux F, Villoutreix BO, Cayuela JM, Guilhot J, Preudhomme C, Guilhot F, Poyet JL, Rousselot P. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget. 2015 Nov 3;6(34):36269-77. doi: 10.18632/oncotarget.5915.
- Delord M, Rousselot P, Cayuela JM, Sigaux F, Guilhot J, Preudhomme C, Guilhot F, Loiseau P, Raffoux E, Geromin D, Genin E, Calvo F, Bruzzoni-Giovanelli H. High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients. Oncotarget. 2013 Oct;4(10):1582-91. doi: 10.18632/oncotarget.1050.
- Johnson-Ansah H, Guilhot J, Rousselot P, Rea D, Legros L, Rigal-Huguet F, Nicolini FE, Mahon FX, Preudhomme C, Guilhot F. Tolerability and efficacy of pegylated interferon-alpha-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. Cancer. 2013 Dec 15;119(24):4284-9. doi: 10.1002/cncr.28328. Epub 2013 Sep 16.
- Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, Guilhot F; SPIRIT Investigators; France Intergroupe des Leucemies Myeloides Chroniques (Fi-LMC). Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010 Dec 23;363(26):2511-21. doi: 10.1056/NEJMoa1004095.
研究記録日
主要日程の研究
研究開始
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- SPIRIT
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
Imatinib mesylate 400 mgの臨床試験
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Dr. Reddy's Laboratories LimitedXenoPort, Inc.完了
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.完了