Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen | Experimental | 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. |
|
| Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen | Placebo Comparator | 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. |
|
| Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HMPL-760 planned dose 1 | Drug | HMPL-760 planned dose 1 daily (QD) orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). | Up to approximately 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | 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 |
| Complete response (CR) rate |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker assessment | 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 |
| Metabolite analysis of HMPL-760 in combination with R-GemOx |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Weili Zhao | Ruijin Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fujian Medical University Union Hospital | Fuzhou | Fujian | China | |||
| Sun Yat-sen University Cancer Center |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen | Placebo Comparator | 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 | Drug | 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. |
|
|
| HMPL-760 placebo planned dose 1 | Drug | HMPL-760 placebo planned dose 1 daily (QD) orally |
|
| HMPL-760 planned dose 2 | Drug | HMPL-760 planned dose 2 daily (QD) orally |
|
| HMPL-760 placebo planned dose 2 | Drug | HMPL-760 placebo planned dose 2 daily (QD) orally |
|
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 |
| Duration of response (DoR) | 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 |
| Clinical benefit rate (CBR) | Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). | Up to approximately 2 years |
| Time to response (TTR) | 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 |
| Overall survival (OS) | Overall Survival (OS) is defined as the time from randomization to death due to any cause. | Up to approximately 2 years |
| Safety Endpoints of adverse events | 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 |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | Trough plasma concentration (Ctrough) of drug | At the end of Cycle 7 (each cycle is 21 days) |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | 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) |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | Time of maximum observed concentration at steady-state(Tmax,ss) of drug | At the end of Cycle 7 (each cycle is 21 days) |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | 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) |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | Apparent clearance at steady-state (CLss/F) of drug (if applicable) | At the end of Cycle 7 (each cycle is 21 days) |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | 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) |
Analysis metabolite of HMPL-760 in combination with R-GemOx |
| At the end of Cycle 7 (each cycle is 21 days) |
| Guangzhou |
| Guangdong |
| China |
| Guangxi Medical University Cancer Hospital | Nanning | Guangxi | China |
| Wuhan Union Hospital of China | Wuhan | Hebei | China |
| Harbin First Hospital | Harbin | Heilongjiang | China |
| Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | China |
| Henan Cancer Hospital | Zhengzhou | Henan | China |
| The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan | China |
| Hunan Cancer Hospital | Changsha | Hunan | China |
| Jiangxi Cancer Hospital | Nanchang | Jiangxi | China |
| The First Affiliated Hospital of Nanchang University | Nanchang | Jiangxi | China |
| Shengjing Hospital of China Medical University | Shenyang | Liaoning | China |
| Shandong Cancer Hospital & Institute | Jinan | Shandong | China |
| Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai Municipality | China |
| West China Hospital of Sichuan University | Chengdu | Sichuan | China |
| Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College | Tianjin | Tianjin Municipality | China |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D000093542 | Gemcitabine |
| D007267 | Injections |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
Not provided
Not provided