Phase I Study of FXS0683 in the Treatment of Blood Tumors (FXS0683-001)
A Multicenter, Open, Single-arm Phase I Dose-escalation and Dose-expansion Clinical Study: Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of FXS0683 Tablets in Patients With Relapsed or Refractory Hematologic Malignancies.
調査の概要
詳細な説明
This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 tablets in participants with relapsed or refractory hematologic malignancies, designed to evaluate safety, tolerability, PK, and preliminary antitumor activity.The study consists of a dose-escalation phase and a dose-expansion phase. The primary objective of dose escalation is to assess safety and tolerability and to determine the MTD and/or RP2D. Dose escalation will follow an accelerated titration design combined with a Bayesian Optimal Interval (BOIN) design. The initial cohort will enroll one participant; if a treatment-related adverse event of Grade ≥2 occurs during the dose-limiting toxicity (DLT) observation period, the cohort will transition to a BOIN design and expand to include additional participants. Dose escalation may proceed in the absence of DLTs among evaluable participants.
The dose-expansion phase is intended to further evaluate safety and preliminary efficacy at selected dose level(s). Expansion may be initiated based on emerging safety, tolerability, and PK data from the dose-escalation phase without requiring completion of all escalation cohorts.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前:Lugui Qiu
- 電話番号:86 022-23608108
- メール:qiulg@ihcams.ac.cn
研究連絡先のバックアップ
- 名前:Bo Jiang
- 電話番号:86 022-23608381
- メール:jiangbo@ihcams.ac.cn
研究場所
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Tianjin Municipality
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Tianjin、Tianjin Municipality、中国、301600
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS)
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コンタクト:
- Shuo Chen
- 電話番号:86 022-23608381
- メール:gcp@ihcams.ac.cn
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Voluntary participation in the clinical trial and signing of the ICF.
- Age ≥ 18 years, regardless of gender.
- Dose escalation phase: Patients with mature B-cell malignancies diagnosed per the 2017 WHO classification who have failed standard therapies and have no appropriate treatment options. Dose expansion phase: Patients with B-cell lymphoma (2017 WHO), myeloid malignancies (2022 WHO), or acute lymphoblastic leukemia.
- Dose escalation phase: Evaluable disease. Dose expansion phase: For B-cell lymphoma, at least one measurable lesion per Lugano 2014 criteria.
- Patients must be willing to undergo bone marrow aspiration and/or biopsy.
- ECOG performance status of 0-1 (dose escalation phase) or 0-2 (dose expansion phase).
- Expected survival time ≥3 months.
- Adequate bone marrow function during screening, as defined by local laboratory reference ranges, without growth factor support.
- Adequate organ function, defined by laboratory values within 7 days prior to the first dose.
- Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception from signing the ICF until 6 months after the last dose.
- Patients at high risk of tumor lysis syndrome (TLS), defined as absolute lymphocyte count (ALC) ≥25×10⁹/L with ≥1 measurable lymph node ≥5 cm or any node ≥10 cm, must be willing to comply with TLS prophylaxis and monitoring requirements.
- Patients must be able to comply with the study procedures and visit schedule.
Exclusion Criteria:
- Burkitt lymphoma/leukemia, plasma cell myeloma, or plasmablastic lymphoma.
- Acute promyelocytic leukemia (APL) or BCR-ABL positive AML patients, or patients with a history of myeloproliferative neoplasms (MPN).
- Use of cytotoxic agents, investigational drugs, or other antitumor therapies within 14 days or 5 half-lives prior to the first dose; or immunotherapy, antibody-based or peptide-based therapies, or live vaccines within 4 weeks prior to the first dose.
- Patients who received any therapeutic surgery other than diagnosis, biopsy, or drainage within 4 weeks before the first dose, or patients expected to undergo major surgery during the study. Patients who underwent drainage or placement of drainage tubes within 4 weeks before the first dose must have symptoms/signs alleviated and not require prophylactic or therapeutic antibiotics.
- Patients who received systemic radiotherapy or palliative local radiotherapy within 4 weeks before the first dose.
- Toxicity from previous anticancer treatment has not recovered to ≤ grade 2, except for hair loss and pigmentation.
- Prior allogeneic stem cell transplantation; or autologous stem cell transplantation or CAR-T therapy within 3 months prior to the first dose.
- Patients with lymphoma/leukemia that has infiltrated the central nervous system.
- Patients with dysphagia or a history of severe gastrointestinal diseases and whose related symptoms cannot be reasonably controlled; or patients with gastrointestinal diseases affecting drug absorption or other malabsorption conditions.
- Active or clinically significant cardiovascular or cerebrovascular disease.
- Patients with interstitial lung disease or a history of pulmonary interstitial fibrosis; or evidence of active pneumonia found on screening chest CT scan.
- Patients with congenital immunodeficiency disorders or active autoimmune diseases, including but not limited to those with active and uncontrolled autoimmune cytopenias lasting ≥2 weeks, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
- Patients with coagulation disorders.
- Patients with a history of severe allergies or allergies to any active or inactive component of the study drug.
- Patients with uncontrolled systemic infections within 2 weeks before the first dose; hepatitis B surface antigen positive with hepatitis B virus DNA >1000 IU/ml; HCV antibody positive with HCV RNA positive; HIV antibody positive.
- Other primary malignancies within 5 years prior to enrollment, except for adequately treated basal or squamous cell skin cancer or carcinoma in situ.
- Patients who still require systemic immunosuppressive agents or systemic corticosteroids within 2 weeks before the study drug.
- Pregnant or breastfeeding women.
- Any other serious or uncontrolled acute or chronic disease or laboratory abnormality or other reasons deemed unsuitable for participation in this clinical trial by the investigator.
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 |
|---|---|
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実験的:FXS0683
This is a first-in-human, multicenter, open-label, single-arm Phase I study consisting of dose-escalation and dose-expansion phases.
FXS0683 will be administered orally once daily at assigned dose levels in 28-day cycles.
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FXS0683 is a potent and highly selective BCL-2 inhibitor
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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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Number of participants with DLTs
時間枠:At the end of Cycle 1 (each cycle is 28 days).
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A DLT is defined as any adverse event or laboratory abnormality occurring during the DLT observation period that is assessed as at least possibly related to FXS0683 and meets pre-specified DLT criteria, graded per NCI-CTCAE Version 6.0.
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At the end of Cycle 1 (each cycle is 28 days).
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MTD and/or RP2D
時間枠:Up to approximately 3 years.
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The MTD and/or RP2D will be determined based on the overall assessment of safety, tolerability, PK, and preliminary efficacy data.
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Up to approximately 3 years.
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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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Incidence and Severity of Adverse Events and Clinically Significant Safety Findings
時間枠:From first dose of study drug until 30 days after the last dose.
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Adverse events (AEs) will be summarized, and severity will be graded according to NCI-CTCAE Version 6.0.
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From first dose of study drug until 30 days after the last dose.
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Objective Response Rate (ORR) Of FXS0683 Monotherapy
時間枠:Up to approximately 3 years.
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ORR will be assessed according to disease-specific response criteria (e.g., Lugano 2014, iwCLL 2018, ELN 2022, or IWG 2006), as applicable.
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Up to approximately 3 years.
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
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
- FXS0683-001
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
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