HMPL-760 Puls R-GemOx vs. Placebo Plus R-GemOx -tutkimus uusiutuneessa/refraktaarisessa DLBCL:ssä
Vaiheen II satunnaistettu, kontrolloitu tutkimus HMPL-760 Plus R-GemOxin tehon, turvallisuuden ja farmakokinetiikkaa vastaan verrattuna Placebo Plus R-GemOx:iin potilailla, joilla on uusiutunut/refraktiivinen diffuusi suuri B-solulymfooma (R/R DLBCL)
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).
Tutkimuksen yleiskatsaus
Tila
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
-
-
Fujian
-
Fuzhou, Fujian, Kiina
- Fujian Medical University Union Hospital
-
-
Guangdong
-
Guangzhou, Guangdong, Kiina
- Sun Yat-sen University Cancer Center
-
-
Guangxi
-
Nanning, Guangxi, Kiina
- Guangxi Medical University Cancer Hospital
-
-
Hebei
-
Wuhan, Hebei, Kiina
- Wuhan Union Hospital of China
-
-
Heilongjiang
-
Harbin, Heilongjiang, Kiina
- Harbin Medical University Cancer Hospital
-
Harbin, Heilongjiang, Kiina
- Harbin First Hospital
-
-
Henan
-
Zhengzhou, Henan, Kiina
- Henan Cancer Hospital
-
Zhengzhou, Henan, Kiina
- The First Affiliated Hospital of Zhengzhou University
-
-
Hunan
-
Changsha, Hunan, Kiina
- Hunan Cancer Hospital
-
-
Jiangxi
-
Nanchang, Jiangxi, Kiina
- Jiangxi Cancer Hospital
-
Nanchang, Jiangxi, Kiina
- The First Affiliated Hospital of Nanchang University
-
-
Liaoning
-
Shenyang, Liaoning, Kiina
- Shengjing Hospital of China Medical University
-
-
Shandong
-
Jinan, Shandong, Kiina
- Shandong Cancer Hospital & Institute
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, Kiina
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
-
-
Sichuan
-
Chengdu, Sichuan, Kiina
- West China Hospital of Sichuan University
-
-
Tianjin Municipality
-
Tianjin, Tianjin Municipality, Kiina
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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;
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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.
Muut nimet:
|
|
Placebo Comparator: 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.
Muut nimet:
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
Kokeellinen: 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.
Muut nimet:
HMPL-760 planned dose 2 daily (QD) orally |
|
Placebo Comparator: 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.
Muut nimet:
HMPL-760 placebo planned dose 2 daily (QD) orally |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Progression-free survival (PFS)
Aikaikkuna: Up to approximately 2 years
|
Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Up to approximately 2 years
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Objective Response Rate (ORR)
Aikaikkuna: 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. |
Up to approximately 2 years
|
|
Complete response (CR) rate
Aikaikkuna: 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. |
Up to approximately 2 years
|
|
Duration of response (DoR)
Aikaikkuna: 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. |
Up to approximately 2 years
|
|
Clinical benefit rate (CBR)
Aikaikkuna: Up to approximately 2 years
|
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)
Aikaikkuna: 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. |
Up to approximately 2 years
|
|
Overall survival (OS)
Aikaikkuna: Up to approximately 2 years
|
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
Aikaikkuna: 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). |
Up to approximately 2 years
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Aikaikkuna: At the end of Cycle 7 (each cycle is 21 days)
|
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
Aikaikkuna: At the end of Cycle 7 (each cycle is 21 days)
|
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
Aikaikkuna: At the end of Cycle 7 (each cycle is 21 days)
|
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
Aikaikkuna: 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)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Aikaikkuna: 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)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Aikaikkuna: 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)
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Biomarker assessment
Aikaikkuna: 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. |
Up to approximately 2 years
|
|
Metabolite analysis of HMPL-760 in combination with R-GemOx
Aikaikkuna: 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)
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Weili Zhao, Ruijin Hospital
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat
- Immuunijärjestelmän sairaudet
- Neoplasmat histologisen tyypin mukaan
- Lymfaattiset sairaudet
- Lymfoproliferatiiviset häiriöt
- Immunoproliferatiiviset häiriöt
- Lymfooma, non-Hodgkin
- Lymfooma, B-solu
- Lymfooma
- Hemic- ja imusuutteet
- Lymfooma, suuri B-solu, diffuusi
- Aminohapot, peptidit ja proteiinit
- Proteiinit
- Heterosykliset yhdisteet, 1-rengas
- Heterosykliset yhdisteet
- Terapeuttiset lääkkeet
- Lämpötilahallinnon reitit
- Lääkehoito
- Vasta -aineet, monoklonaalinen
- Vasta -aineet
- Immunoglobuliinit
- Immunoproteiinit
- Veriproteiinit
- Seerumin globuliinit
- Globuliinit
- Deoksisytidiini
- Syytidiini
- Pyrimidiininnukleosidit
- Pyrimidiinit
- Vasta-aineet, monoklonaalinen, hiiren johdettu
- Rituksimabi
- Gemsitabiini
- Injektiot
Muut tutkimustunnusnumerot
- 2024-760-00CH1
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .