A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome
2015年11月11日 更新者：Hoffmann-La Roche
A PHASE IB/II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF VISMODEGIB IN RELAPSED/REFRACTORY ACUTE MYELOGENOUS LEUKEMIA (AML) AND RELAPSED/REFRACTORY HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS)
This study will assess the safety and efficacy of vismodegib in patients with relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150 mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in combination with cytarabine 20 mg subcutaneously for 10 days.
Anticipated time on study treatment is until disease progression, intolerable toxicity, or patient withdrawal of consent.
調査の概要
研究の種類
介入
入学 (実際)
38
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Stanford、California、アメリカ、94305
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
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Missouri
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Kansas City、Missouri、アメリカ、64131
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New York
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New York、New York、アメリカ、10065
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Texas
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Houston、Texas、アメリカ、77030
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Alberta
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Edmonton、Alberta、カナダ、T6L5X8
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Ontario
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Toronto、Ontario、カナダ、M5G 2M9
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Quebec
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Montreal、Quebec、カナダ、H1T 2M4
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Montreal、Quebec、カナダ、H3T 1E2
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Braunschweig、ドイツ、38114
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Essen、ドイツ、45122
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Hamburg、ドイツ、20246
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Heidelberg、ドイツ、69120
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Münster、ドイツ、48149
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Adult patients, >/= 18 years of age
- Patients with documented relapsed or refractory AML, except acute promyelocytic leukemia (APL [M3 subtype]), or relapsed or refractory high-risk MDS (high-risk MDS defined as International Prognostic Scoring System (IPSS) Int-2 or high and >/= 10% blasts in bone marrow)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Negative serum pregnancy test for women of childbearing potential and use of two forms of contraception while enrolled in the study and for 7 months after the patient discontinues from study
- Male patients with female partners of childbearing potential must agree to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 2 months after the last dose of vismodegib
- All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade </= 2 prior to starting therapy
- Adequate hepatic and renal function
Exclusion Criteria:
- Prior treatment with a Hh pathway inhibitor
- Prior therapy for the treatment of malignancy within 14 days of Day 1, with the exception of:
Hydroxyurea in patients who need to continue this agent to maintain white blood cell (WBC) counts </= 50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study
- Current evidence of active central nervous system (CNS) leukemia
- Any other active malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix)
- Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication (does not include stable, lone atrial fibrillation), or myocardial infarction </= 6 months before study treatment start Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
- Pregnant or breast-feeding women
- Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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 |
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実験的：ビスモデギブ
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Cohort 2: 20 mg sc daily for 10 days starting Day 1, with a possible further cycle of 20 mg sc daily for 5 days starting no earlier than Day 29
Cohorts 1 and 2: 150 mg orally daily
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 |
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Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
時間枠：Week 8
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CR was defined as achieved if the neutrophils count was greater than (>) 1000 cells per microliter (µL), platelets count >100000/µL, bone marrow blasts percentage (%) less than (<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD).
CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils >1000 cells/µL or Not applicable [NA] or platelets count >100000/µL or NA), bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD.
MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD.
PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.
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Week 8
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
時間枠：Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
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CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD.
CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD.
MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD.
PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.
The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.
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Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
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Duration of Overall Response (DOR)
時間枠：Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
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DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria [CR or CRi or MLFS or PR] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug).
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Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
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Median Overall Survival (OS) Time
時間枠：Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
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OS was defined as the time from start of study drug to death from any cause.
OS was estimated using Kaplan-Meier analysis.
Participants alive at the last date known to be alive were censored for the analysis.
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Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
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Percentage of Participants With an Event of Death During the Study
時間枠：Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
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Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
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Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib
時間枠：Predose on Days 8, 29 and 57
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PK data was planned to be reported only if the results of Cohort 2 are available.
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Predose on Days 8, 29 and 57
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Area Under the Concentration-time Curve (AUC) of Cytarabine
時間枠：Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
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PK data was planned to be reported only if the results of Cohort 2 are available.
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Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2013年9月1日
一次修了 (実際)
2014年11月1日
研究の完了 (実際)
2014年11月1日
試験登録日
最初に提出
2013年6月11日
QC基準を満たした最初の提出物
2013年6月14日
最初の投稿 (見積もり)
2013年6月19日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年12月15日
QC基準を満たした最後の更新が送信されました
2015年11月11日
最終確認日
2015年11月1日
詳しくは
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。