Clinical trial NCT04849351: Clinical Study of HMPL-689 for Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma
Official title: A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients With Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
Follicular Lymphoma
Keywords: Marginal Zone Lymphoma
Follicular Lymphoma
Phosphatidylinositol 3-kinase inhibitor
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2021-04-19
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients with Relapsed/Refractory Marginal Zone Lymphoma (MZL) and Follicular Lymphoma (FL)

Detailed description: This is a multi-center, single-arm, open-label clinical study to evaluate the oral therapy with HMPL-689 in patients with relapsed / refractory MZL and FL. Relapse / refractory is defined as such a situation when a patient has not achieved response (CR or PR) after the latest line of systemic treatment, or has disease progress (PD) or relapse after achieving response. Two (2) cohorts of patients will be enrolled in this study:

Cohort 1: approximately 81 patients with histologically confirmed MZL

Cohort 2: approximately 104 patients with histologically confirmed FL (pathological grade 1-3a)

All patients are to receive monotherapy of HMPL-689 30 mg once a day (QD) continuously in 28-day treatment cycles until PD / recurrence, patient death, intolerable toxicity, initiation of other antitumor therapy, the patient unable to further benefit from the study treatment as judged by the investigators, the patient or his/her legal representative's request to withdraw from the clinical study treatment, the patient lost to follow-up or end of the study, whichever comes first.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years;
2. Patients with relapsed/refractory marginal zone lymphoma or follicular lymphoma
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-2;
4. At least one measurable lesion by computerised tomography (CT) / magnetic resonance imaging (MRI) (the longest diameter of nodal lesion \> 1.5 cm or extranodal lesion \> 1 cm);
5. Expected survival of more than 12 weeks;

Exclusion Criteria:

1. Having lymphoma with central nervous system (CNS) or cerebral pia mater invasion;
2. Known histologic transformation to aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL);
3. Prior use of any phosphatidylinositol 3-kinase (PI3K) inhibitor;
4. Inadequate organ function of liver and kidney;
5. Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV);
6. Having received systemic antitumor therapy or radiotherapy within 4 weeks prior to the first dose of the investigational product;
7. Toxicity of previous antitumor therapy not recovered to CTCAE grade ≤ 1, except alopecia, prior to the first dose of the investigational product;
8. Complicated with uncontrolled systemic infection requiring intravenous antibiotic treatment;
9. Pregnant (positive serum pregnancy test) or lactating women;
10. Any other disease, metabolic abnormality, physical examination abnormality or clinically significant laboratory test abnormality, one disease or state providing a reason to suspect that the subject is not suitable for HMPL-689 at the investigator's discretion, or one condition that will affect interpretation of the study results or bring the subject at high risk.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
Secondary outcomes:
measure: Complete response (CR) rate
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
measure: Progression-free survival (PFS)
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
measure: Time to response (TTR)
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
measure: Duration of response (DoR)
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
measure: Overall survival (OS)
timeFrame: Baseline up to the last patient has completed 12 months after treatment.
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Chao-yang Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing GoBroad Boren Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Hebei
city: Shijia Zhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Ha'erbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Ha'erbin
country: China
facility: The First Hospital of Harbin
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: People's Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Huaihua
country: China
facility: The Second People's Hospital of Huaihua
state: Hunan
city: Yongzhou
country: China
facility: The Central Hospital of YongZhou
state: Hunan
city: Nantong
country: China
facility: The First People's Hospital of Nantong
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Suzhou University
state: Jiangsu
city: Gannan
country: China
facility: The First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Ganzhou
country: China
facility: Ganzhou People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Provincial Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Binzhou
country: China
facility: Affiliated Hospital of Binzhou Medical University
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: The affiliated hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital, Tongji University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Fudan University
name: junning Cao, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-sen University
name: Zhiming Li, post-doc
role: PRINCIPAL_INVESTIGATOR
References: