デシタビンおよびベネトクラクスと標的変異型 IDH1 阻害剤オルタシデニブの併用の第 1b/2 相試験
To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.
調査の概要
詳細な説明
Primary Objectives
- Phase 1b: To determine the safety and tolerability and recommended phase 2 dose (RP2D) of decitabine (either IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib.
- Phase 2: To determine the composite remission rate (CR, CRh and CRi) of decitabine (IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib for newly diagnosed (Arm A) or relapsed/refractory (Arm B) participants with IDH1-mutated myeloid malignancy.
Secondary Objectives
- To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS)
- To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.
- To determine the overall response rate (CR, CRh, CRi, MLFS, and PR)
- To characterize the pharmacokinetic (PK) profiles of venetoclax and olutasidenib in plasma samples (Phase 1b only).
Exploratory Objectives
- To investigate global gene expression profiles, DNA methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Courtney DiNardo, MD
- 電話番号：(713) 794-1141
- メール：cdinardo@mdanderson.org
研究場所
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Florida
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Miami、Florida、アメリカ、33136
- 募集
- University of Miami
-
主任研究者：
- Justin Watts, MD
-
コンタクト：
- Justin Watts, MD
- 電話番号：305-243-8986
- メール：jxw401@med.miami.edu
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Kansas
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Westwood、Kansas、アメリカ、66205
- 募集
- The University of Kansas Medical Center
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コンタクト：
- Yacoub Abdulraheem, MD
- メール：ayacoub@kumc.edu
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主任研究者：
- Yacoub Abdulraheem, MD
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- 募集
- Dana-Farber Cancer Institute
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主任研究者：
- Jacqueline Garcia, MD
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コンタクト：
- Jacqueline Garcia, MD
- 電話番号：617-632-6349
- メール：jacqueline_garcia@dfci.harvard.edu
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-
New York
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Buffalo、New York、アメリカ、14263
- 募集
- Roswell Park
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主任研究者：
- Eunice Wang, MD
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コンタクト：
- Eunice Wang, MD
- メール：eunice.wang@roswellpark.org
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Texas
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Houston、Texas、アメリカ、77030
- 募集
- MD Anderson Cancer Center
-
コンタクト：
- Courtney DiNardo, MD
- 電話番号：713-794-1141
- メール：cdinardo@mdanderson.org
-
主任研究者：
- Courtney DiNardo, MD
-
-
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:
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Age > 18 years
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Participants must have a documented IDH1 gene mutation
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Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR
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Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only)
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To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
- Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
- Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%).
- Creatinine clearance ≥30 mL/min to <45 mL/min.
- Moderate hepatic impairment with total bilirubin >1.5 to .3.0 x upper limit of normal (ULN)
- ECOG performance status of 2 or 3
- Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy
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Eastern Cooperative Oncology Group (ECOG) Performance Status </=2 (unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5e above)
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Adequate renal function including creatinine < 1.5, unless related to the disease or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5c above.
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Adequate hepatic function (direct bilirubin < 2x upper limit of normal (ULN) unless increase is due to Gilbert fs disease or leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible, or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5d above)
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In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
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Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
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Willing and able to provide informed consent.
Exclusion Criteria:
- Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML).
- Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
- Participants with active, uncontrolled leukemia involvement of the CNS
- Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant including active cGVHD requiring topic therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to start of study treatment.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
- Participant has a white blood cell count > 25 x 10^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.)
- Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
A) Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).
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）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Part 1
Participants enrolled in Part 1, the dose of venetoclax/decitabine you receive will depend on when you join this study. Up to 3 dose levels will be tested. Up to 6 participants will be enrolled at each dose level. - All participants will receive the same dose level of olutasidenib. |
Given by PO
他の名前：
Given by IV
他の名前：
Given by PO Given by PO
他の名前：
|
|
実験的：Part 2
Participants enrolled in Part 2, you will receive venetoclax/decitabine at the recommended dose that was found in Part 1. - All participants will receive the same dose level of olutasidenib. |
Given by PO
他の名前：
Given by IV
他の名前：
Given by PO Given by PO
他の名前：
|
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 |
|---|---|---|
|
Safety and adverse events (AEs)
時間枠：Through study completion; an average of 1 year.
|
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
Through study completion; an average of 1 year.
|
協力者と研究者
捜査官
- 主任研究者：Courtney DiNardo, MD、M.D. Anderson Cancer Center
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
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 (実際)
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
- 2024-0180
- NCI-2024-04807 (その他の識別子：NCI-CTRP Clinical Registry)
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
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。