Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia (HEMOS AML 0106)
Phase II, Open-Label, Multi-centre, 2-part Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Conventional Chemotherapy ( >18 Years) or in Patients With Acute Myeloid Leukemia in First Relapse ( >60 Years)
This is one of the first studies of combination of Zarnestra plus Velcade in man. A primary objective of the study is therefore to assess the safety and tolerability of multiple doses of Zarnestra plus Velcade in patients with AML.
New treatments for patients that are untreatable with intensive chemotherapy aged de novo AML patients or post-relapse AML are urgently required since, at present, many of the drugs used for second line therapy are the same as those used for first induction and response rates are much lower.
- The following evidence suggests that Velcade plus Zarnestra can be an attractive therapeutic combination for: AML patients.
- Affymetrix gene profiling data showed expression of NFkB1 in all of 5 myeloid cell lines cell lines tested and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy)
- Preclinical evidence showed that AML cells in suspension culture were prevented to develop de novo drug resistance and mediated drug resistance.
In Part B additional patients with AML will be treated to further characterize the tolerability,biological effects, and clinical efficacy of the combination Velcade plus Zarnestra. Patients on treatment for AML will undergo regular bone marrow aspirates and biopsies to assess responses to treatment. This will facilitate frequent assessment of biological endpoints (reduction in expression and phosphorylation of IKKb kinase, and downstream markers of signalling along with apoptosis, survival, proliferation and cellular size and ploidy) will be made in an attempt to confirm that the desired biological activity has been achieved at the maximum tolerated dose.
調査の概要
研究の種類
入学 (予想される)
段階
- フェーズ2
連絡先と場所
研究場所
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Bologna、イタリア、40138
- 募集
- Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi
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コンタクト：
- Giovanni Martinelli, MD
- 電話番号：+039 051 6363829
- メール：martg@tin.it
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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:
- Provision of written informed consent
- Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy
- Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years)
- WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy
- Negative pregnancy test or evidence of post-menopausal status for female patients.
- RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only)
Exclusion Criteria:
- Serum bilirubin 2 x> Upper Limit of Normal (ULN)
- Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN
- Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault)
- Patients with AML of FAB M3 classification (APL)
- Patients with a history of another primary malignancy within the previous 1 year other than basal cell carcinoma or carcinoma in situ, the patient is in remission
- Any clinically defined central nervous system AML.
- Participation in an investigational drug study within the 30 days prior to entry
- Evidence of uncontrolled infection or CNS-Hemorrhagic
- Patients with documented cases of human immunodeficiency virus (HIV)
- Peripheral Neuropathy or Neuropathic Pain grade > or = 2
- Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
- Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 7,NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only)
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：非ランダム化
- 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）
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 |
時間枠 |
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PART A: Assess the safety and tolerability of combined use of Zarnestra plus multiple ascending doses of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in first or subsequent relapse ( >60 years).(COMPLETED)
時間枠：August 2007
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August 2007
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Part B.1: Assess the effect of Tipifarnib plus the defined in part A dose of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in Patients in first or subsequent relapse ( >60 years) (COMPLETED)
時間枠：December 2008
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December 2008
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Part B.2: Evaluate the overall response (CR, PR, HI) of patients with a RASGRP1/APTX gene expression ratio > 10, identified as predictive of a good clinical response to tipifarnib in patients with de novo AML unfit for conventional chemotherapy.
時間枠：June 2010
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June 2010
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二次結果の測定
結果測定 |
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To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB
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Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis,
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Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip.
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Giovanni Martinelli, MD、Istituto di Ematologia ed Oncologia Medica "L.eA.Seràgnoli" Policlinico S.Orsola-Malpighi di Bologna
研究記録日
主要日程の研究
研究開始
一次修了
研究の完了
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 (見積もり)
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
その他の研究ID番号
- HEMOS AML 0106
- EudraCT 2007-000273-35
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。
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