Study of INCB053914 in Subjects With Advanced Malignancies
2021年11月9日 更新者：Incyte Corporation
A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies.
The study will be conducted in 4 parts.
Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study).
Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s).
Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).
調査の概要
状態
終了しました
条件
研究の種類
介入
入学 (実際)
97
段階
- フェーズ2
- フェーズ 1
アクセスの拡大
承認済み 一般販売用。
拡張アクセス記録をご覧ください。
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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Arizona
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Tucson、Arizona、アメリカ、85719
- The University of Arizona Cancer Center
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California
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Sacramento、California、アメリカ、95817
- UC Davis Comprehensive Cancer Center
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Santa Monica、California、アメリカ、90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven、Connecticut、アメリカ、06511
- Yale University
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Florida
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Jacksonville、Florida、アメリカ、32224
- Mayo Clinic Florida
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Sarasota、Florida、アメリカ、33916
- Florida Cancer Specialists & Research Institute
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Tampa、Florida、アメリカ、33612
- H. Lee Moffitt Cancer Center & Research Institute
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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、21201
- University of Maryland
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha、Nebraska、アメリカ、69198
- University of Nebraska Medical Center
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Ohio
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Cincinnati、Ohio、アメリカ、45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
- Stephenson Cancer Center
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt University Medical Center
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Nashville、Tennessee、アメリカ、37203
- Tennessee Oncology
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Texas
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Austin、Texas、アメリカ、78705
- Texas Oncology
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Tyler、Texas、アメリカ、75702
- Texas Oncology
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Wisconsin
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Milwaukee、Wisconsin、アメリカ、53226
- Medical College of Wisconsin
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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:
- Aged 18 years or older
- Confirmed diagnosis of select advanced malignancy
Parts 1 and 2:
- Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
- Not currently a candidate for curative treatment
Parts 3 and 4:
- Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Eastern Cooperative Oncology Group (ECOG) performance status
- Part 1: 0 or 1
- Parts 2, 3 and 4: 0, 1, or 2
- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.
Exclusion Criteria:
- Inadequate bone marrow or organ function
- Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
- Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
- Prior receipt of a PIM inhibitor
- Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
- Screening corrected QT interval (QTc) interval > 470 milliseconds
- Radiotherapy within the 2 weeks prior to initiation of treatment
- Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment
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：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）
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：Parts 1 and 2: INCB053914 100 mg QD
INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
実験的：Parts 3 and 4: INCB053914 + Azacitidine
Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Azacitidine dose will be 75 mg/m^2.
Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
他の名前：
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実験的：Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Cytarabine dose will be 1 g/m^2.
Cytarabine will be administered as an intravenous (IV) infusion.
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実験的：Parts 3 and 4: INCB053914 + Ruxolitinib
Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
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実験的：Parts 1 and 2: INCB053914 50 mg
INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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実験的：Parts 1 and 2: INB053914 65 mg
INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
実験的：Parts 1 and 2: INB053914 80 mg
INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
実験的：Parts 1 and 2: INB053914 100 mg BID
INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
実験的：Parts 1 and 2: INB053914 115 mg
INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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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Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
時間枠：Approximately 7 months
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Approximately 7 months
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
時間枠：Approximately 2 months
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The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
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Approximately 2 months
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
時間枠：Approximately 6 months
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The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
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Approximately 6 months
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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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Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
時間枠：1 month
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Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
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1 month
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Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
時間枠：Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
時間枠：Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
時間枠：Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
時間枠：Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
時間枠：Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
時間枠：Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
時間枠：Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
時間枠：Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
時間枠：Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
時間枠：Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
時間枠：Cycle 1 Day 8
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Cycle 1 Day 8
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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 (実際)
2015年12月29日
一次修了 (実際)
2020年8月11日
研究の完了 (実際)
2020年8月11日
試験登録日
最初に提出
2015年10月26日
QC基準を満たした最初の提出物
2015年10月26日
最初の投稿 (見積もり)
2015年10月27日
学習記録の更新
投稿された最後の更新 (実際)
2021年12月8日
QC基準を満たした最後の更新が送信されました
2021年11月9日
最終確認日
2021年11月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- INCB 53914-101
医薬品およびデバイス情報、研究文書
米国FDA規制機器製品の研究
いいえ
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。