再発/難治性 DLBCL における HMPL-760 パルス R-GemOx とプラセボ + R-GemOx の研究
再発性/難治性びまん性大細胞型B細胞リンパ腫(R/R DLBCL)患者におけるHMPL-760プラスR-GemOxとプラセボプラスR-GemOxの有効性、安全性、および薬物動態を評価する第II相ランダム化比較試験
The goal of this study is to evaluate the efficacy of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).
調査の概要
状態
詳細な説明
A Phase II Randomized, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 in Combination with R-GemOx versus Placebo in Combination with R-GemOx in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.
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
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Fujian
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Fuzhou、Fujian、中国
- Fujian Medical University Union Hospital
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Guangdong
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Guangzhou、Guangdong、中国
- Sun Yat-sen University Cancer Center
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Guangxi
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Nanning、Guangxi、中国
- Guangxi Medical University Cancer Hospital
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Hebei
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Wuhan、Hebei、中国
- Wuhan Union Hospital of China
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Heilongjiang
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Harbin、Heilongjiang、中国
- Harbin Medical University Cancer Hospital
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Harbin、Heilongjiang、中国
- Harbin First Hospital
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Henan
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Zhengzhou、Henan、中国
- Henan Cancer Hospital
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Zhengzhou、Henan、中国
- The First Affiliated Hospital of Zhengzhou University
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Hunan
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Changsha、Hunan、中国
- Hunan Cancer Hospital
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Jiangxi
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Nanchang、Jiangxi、中国
- Jiangxi Cancer Hospital
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Nanchang、Jiangxi、中国
- The First Affiliated Hospital of Nanchang University
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Liaoning
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Shenyang、Liaoning、中国
- Shengjing Hospital of China Medical University
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Shandong
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Jinan、Shandong、中国
- Shandong Cancer Hospital & Institute
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Shanghai Municipality
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Shanghai、Shanghai Municipality、中国
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Sichuan
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Chengdu、Sichuan、中国
- West China Hospital of Sichuan University
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Tianjin Municipality
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Tianjin、Tianjin Municipality、中国
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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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:
- Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
- Age ≥18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2;
- Histopathologically confirmed diagnosis of DLBCL;
- The investigator judges that the patient's current condition requires further treatment;
- Patients should have at least one bi-dimensionally measurable lesion;
- Expected survival is more than 12 weeks;
Exclusion Criteria:
- Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
- Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
- Organ insufficiency;
- Currently known history of liver disease, including cirrhosis, alcoholic liver, known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV):
- History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
- Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
- Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
- Clinically significant active infection;
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen
Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
HMPL-760 planned dose 1 daily (QD) orally R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
他の名前：
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プラセボコンパレーター：Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
他の名前：
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
実験的：Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
他の名前：
HMPL-760 planned dose 2 daily (QD) orally |
|
プラセボコンパレーター：Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
他の名前：
HMPL-760 placebo planned dose 2 daily (QD) orally |
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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Progression-free survival (PFS)
時間枠：Up to approximately 2 years
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Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Up to approximately 2 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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Objective Response Rate (ORR)
時間枠：Up to approximately 2 years
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Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator. |
Up to approximately 2 years
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Complete response (CR) rate
時間枠：Up to approximately 2 years
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Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator. |
Up to approximately 2 years
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Duration of response (DoR)
時間枠：Up to approximately 2 years
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For patients who reached complete response (CR) or partial response (PR), Duration of Response (DoR) is defined as the time from the first CR or PR until disease progression or death due to any cause, whichever occurs first, as assessed by investigator. |
Up to approximately 2 years
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Clinical benefit rate (CBR)
時間枠：Up to approximately 2 years
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Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). |
Up to approximately 2 years
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Time to response (TTR)
時間枠：Up to approximately 2 years
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Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR), as assessed by investigator. |
Up to approximately 2 years
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Overall survival (OS)
時間枠：Up to approximately 2 years
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Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Up to approximately 2 years
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Safety Endpoints of adverse events
時間枠：Up to approximately 2 years
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Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of serious adverse events (SAEs), incidence of TEAEs leading to permanent discontinuation, dose interruption, and dose reduction, and their correlation to study drug. The severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0). |
Up to approximately 2 years
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
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Trough plasma concentration (Ctrough) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
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Maximum observed concentration, occurring at time Tmax at steady-state (Cmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
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Time of maximum observed concentration at steady-state(Tmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
|
The partial area from dosing time to dosing time plus Tau at steady-state (AUCss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
|
Apparent clearance at steady-state (CLss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
|
Apparent volume of distribution at steady-state (Vz,ss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Biomarker assessment
時間枠：Up to approximately 2 years
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To evaluate the correlation between potential biomarkers and the prognosis of patients treated with this regimen. Tumor tissue or blood samples will be examined to detect the gene expression of MYD88. |
Up to approximately 2 years
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Metabolite analysis of HMPL-760 in combination with R-GemOx
時間枠：At the end of Cycle 7 (each cycle is 21 days)
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Analysis metabolite of HMPL-760 in combination with R-GemOx |
At the end of Cycle 7 (each cycle is 21 days)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Weili Zhao、Ruijin Hospital
研究記録日
主要日程の研究
研究開始 (実際)
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 (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
- 2024-760-00CH1
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個々の参加者データ (IPD) を共有する予定はありますか?
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