Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
調査の概要
状態
条件
- 続発性急性骨髄性白血病
- 未治療の成人急性骨髄性白血病
- 成人急性単芽球性白血病
- 成人急性単球性白血病
- Inv(16)(p13.1q22)を伴う成人急性骨髄性白血病; CBFB-MYH11
- 成熟を伴う成人急性骨髄性白血病
- 微少分化型成人急性骨髄性白血病
- T(16;16)(p13.1;q22); を伴う成人急性骨髄性白血病CBFB-MYH11
- 成熟していない成人急性骨髄性白血病
- 成人急性骨髄単球性白血病
- アルキル化剤関連の急性骨髄性白血病
- 成人急性巨核芽球性白血病
- 成人赤白血病
- 成人純粋赤血球性白血病
- T(9;11)(p22;q23); を伴う成人急性骨髄性白血病MLLT3-MLL
- T(8;21)(q22;q22); を伴う成人急性骨髄性白血病RUNX1-RUNX1T1
介入・治療
詳細な説明
PRIMARY OBJECTIVES:
I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.
SECONDARY OBJECTIVES:
I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.
III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.
OUTLINE: This is a multicenter study.
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.
After completion of study therapy, patients are followed up every 30 days.
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
-
-
Florida
-
Tampa、Florida、アメリカ、33612
- Moffitt Cancer Center
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Georgia
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Atlanta、Georgia、アメリカ、30342
- Blood and Marrow Transplant Group of Georgia
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Atlanta、Georgia、アメリカ、30322
- Emory University/Winship Cancer Institute
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Maryland
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Baltimore、Maryland、アメリカ、21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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New York
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New York、New York、アメリカ、10065
- Memorial Sloan-Kettering Cancer Center
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New York、New York、アメリカ、10065
- Weill Medical College of Cornell University
-
-
North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- University of North Carolina
-
-
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:
Previously untreated acute myeloid leukemia (AML) (de novo or secondary)
- No diagnosis of acute promyelocytic leukemia (APL)
- Deemed unsuitable for or refuses standard induction chemotherapy
- RASGRP1:APTX ratio >= 5, through bone marrow screening
- No patients with known leukemic involvement of the central nervous system
- ECOG performance status =< 2
- No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
- Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)
- Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
- ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
- Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- No symptomatic neuropathy of grade 2 or worse
- No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
- No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy AND with a CD4 cell count >= 400/mm^3 are eligible
- No other concurrent cytotoxic or biologic antileukemic therapy
- No patients who are receiving any other investigational agents
Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated
- If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777
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)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21.
Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
|
相関研究
与えられたPO
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
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Complete Remission (CR) Rate
時間枠:From first treatment through follow up period, an expected average of 12 months
|
Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.
AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
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From first treatment through follow up period, an expected average of 12 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Median Overall Survival (OS)
時間枠:From first treatment through follow up period, an expected average of 12 months
|
Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).
|
From first treatment through follow up period, an expected average of 12 months
|
Median 1-Year Survival Rate
時間枠:1 year
|
Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.
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1 year
|
Number of Participants With Relapse Free Survival
時間枠:7 months
|
Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.
|
7 months
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協力者と研究者
捜査官
- 主任研究者:Jeffrey Lancet、Moffitt Cancer Center
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 (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
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2011-02589 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
- U01CA070095 (米国 NIH グラント/契約)
- N01CM00071 (米国 NIH グラント/契約)
- P30CA076292 (米国 NIH グラント/契約)
- N01CM00100 (米国 NIH グラント/契約)
- 16572
- CDR0000699713
- 8977 (その他の識別子:CTEP)
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。
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