Diffuse Large B-cell Lymphoma
Conditions
Interventions
Experimental group:Homoharringtonine
Sponsors
The First Affiliated Hospital, Zhejiang University College of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Phase Ib eligibility criteria 1) Aggressive large B-cell lymphoma with CD20-positive histopathological confirmation; 2) Patients aged 18 years or older, male or female, ECOG score: 0-2; 3) Patients who had previously received first-line standard therapy with primary drug resistance, short-term progression (within 1 year after the end of treatment), or failure to respond to second-line or above standard therapy or relapse; 4) At least one measurable lesion (according to Lugano2014 criteria, measurable lesion was defined as the longest diameter of lymph node lesion >1.5cm in cross-sectional CT images; Or the maximum diameter of extranodal lesions >1.0cm; And FDG-PET positive lesions); 5) Provide signed informed consent and be able to understand and comply with the requirements of the study. Phase II eligibility criteria 1) Histopathologically confirmed CD20-positive diffuse large B-cell lymphoma; 2) Age >=18 years at enrollment, regardless of gender, with an ECOG performance status of 0–3; 3) Disease is refractory to or progresses within one year after first-line standard therapy containing anti-CD20 monoclonal antibodies and anthracycline-based chemotherapy, or has failed or relapsed after second-line or later standard treatment regimens, or has relapsed after autologous hematopoietic stem cell transplantation (more than 6 months post-transplant); 4) At least one measurable lesion present (as defined by the Lugano 2014 response criteria: measurable lesion is defined as a lymph node lesion with a longest diameter >1.5 cm on CT axial imaging, or an extranodal lesion with a longest diameter >1.0 cm, and 18F-FDG PET/CT positive lesion); 5) Able to provide written informed consent and capable of understanding and complying with all study requirements.
Exclusion criteria
Exclusion criteria: Phase Ib exclusion criteria 1) Poor compliance or inability to follow up regularly; 2) Patients have severe organ damage and are not suitable to participate in the trial according to the investigator; 3) Abnormal liver function (total bilirubin > 1.5 times the upper limit of normal, ALT/AST> 2.5 times the upper limit of normal or ALT/AST> 5 times the upper limit of normal in patients with liver involvement), abnormal renal function (serum creatinine > 1.5 times the upper limit of normal); 4) Absolute neutrophil count 2000IU/ml or 104 copies /ml; HCV RNA > 103 copies /ml; 9) Patients with central nervous system metastasis, but central nervous system metastasis without clinical symptoms or with clinical symptoms, disease control after treatment and stable time >=4 weeks; 10) Abnormal cardiac function: baseline QTc=500ms; LVEF 2000 IU/mL or 104 copies/mL, or HCV RNA > 10³ copies/mL; 8)Central nervous system (CNS) metastases; however, patients with asymptomatic CNS metastases or those with symptoms that have been treated and stabilized for >=4 weeks may be eligible; 9)Prior history of allogeneic hematopoietic stem cell transplantation; 10)Cardiac dysfunction: baseline QTc >= 500 ms; LVEF < 45%, or NYHA Class III/IV heart failure; 11)Known severe hypersensitivity to benzyl alcohol or any other components of the study drugs; 12)Requirement for concomitant use of strong CYP3A4 inducers due to medical necessity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate;Dose-Limiting Toxicities (DLT);Maximum Tolerated Dose (MTD);Recommended Phase II Dose (RP2D); | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete Response (CR) Rate;Partial Response (PR) Rate;Progression-Free Survival (PFS);Overall Survival (OS);Safety and Tolerability (Adverse Events); | — |
Countries
China
Contacts
Public ContactXie Wanzhuo; Jin Jie
The First Affiliated Hospital, Zhejiang University College of Medicine
Outcome results
None listed