Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Conditions
Keywords
R-GemOx, R/R DLBCL, HMPL-760
Brief summary
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).
Detailed description
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.
Interventions
DRUGHMPL-760 planned dose 1
HMPL-760 planned dose 1 daily (QD) orally
DRUGR-GemOx
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.
DRUGHMPL-760 placebo planned dose 1
HMPL-760 placebo planned dose 1 daily (QD) orally
DRUGHMPL-760 planned dose 2
HMPL-760 planned dose 2 daily (QD) orally
DRUGHMPL-760 placebo planned dose 2
HMPL-760 placebo planned dose 2 daily (QD) orally
Sponsors
Hutchmed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol; 2. Age ≥18 years; 3. Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2; 4. Histopathologically confirmed diagnosis of DLBCL; 5. The investigator judges that the patient's current condition requires further treatment; 6. Patients should have at least one bi-dimensionally measurable lesion; 7. Expected survival is more than 12 weeks;
Exclusion criteria
1. Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL; 2. Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding; 3. Organ insufficiency; 4. 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): 5. History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug; 6. Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin); 7. Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite); 8. Clinically significant active infection;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to approximately 2 years | Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | Up to approximately 2 years | Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator. |
| Objective Response Rate (ORR) | Up to approximately 2 years | Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator. |
| Duration of response (DoR) | Up to approximately 2 years | 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. |
| Clinical benefit rate (CBR) | Up to approximately 2 years | Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). |
| Safety Endpoints of adverse events | Up to approximately 2 years | 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). |
| Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx | At the end of Cycle 7 (each cycle is 21 days) | Trough plasma concentration (Ctrough) of drug |
| Time to response (TTR) | Up to approximately 2 years | 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. |
| Overall survival (OS) | Up to approximately 2 years | Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarker assessment | Up to approximately 2 years | 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. |
| Metabolite analysis of HMPL-760 in combination with R-GemOx | At the end of Cycle 7 (each cycle is 21 days) | Analysis metabolite of HMPL-760 in combination with R-GemOx |
Countries
China
Outcome results
None listed