Relapsed or refractory B-cell lymphoma
Conditions
Interventions
Experimental group (Phase 1):FCN-338
Experimental group (Phase 2):FCN-338
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects are eligible to be included in the study only if they meet all of the following criteria: 1. Female and male patients aged 18~75 (inclusive); 2. Phase 1 study (dose-escalation stage): Patients with histopathologically confirmed mature B-cell lymphoma as defined based on 2016 updated WHO classification, diffuse large B-cell lymphoma that is unresponsive to at least 2 prior lines of standard treatment, other mature B-cell lymphomas with indications for treatment that are unresponsive to at least 2 prior lines of standard treatment, except chronic lymphocytic leukemia/small cell lymphocytic lymphoma, Burkitt's lymphoma/leukemia, plasma cell myeloma, and plasmablastic lymphoma; Phase 2 study (expansion stage): Patients with histopathologically confirmed mantle cell lymphoma that is unresponsive to prior BTK inhibitor-based treatment or at least 2 lines of standard treatment; 3. Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1 point for Phase 1 study; 0-2 point for Phase 2 study; 4. Expected survival = 12 weeks; 5. Phase 1 study (dose-escalation stage): Patients with evaluable lesions. Phase 2 study(expansion stage): MCL patients (to be evaluated by Lugano criteria) with at least 1 radiographically measurable lesion (i.e. nodal lesions with a long diameter [LDi] > 1.5 cm and extranodal lesions with an LDi > 1.0 cm); 6. Patients with adequate bone marrow independent of growth factor support per local laboratory reference range at Screening as follows: a. Absolute neutrophil count (ANC) = 1.0 × 10^9/L (patients with ANC < 1.0 × 10^9/L due to lymphoma bone marrow infiltration can be eligible based on the investigator's judgment); b. Platelet count = 75 × 10^9/L (Phase 1 study), Platelet count = 50 × 10^9/L (Phase 2 study), without transfusion within 14 days prior to the first dose; c. Hemoglobin = 80 g/L; 7. Left ventricular ejection fraction (LVEF) = 50%; 8. Adequate renal function: Creatinine clearance = 50 mL/min calculated with a 24-hour creatinine clearance or the modified Cockcroft-Gault equation (using ideal body weight [IBM] instead of body weight, see Attachment 7). 9. Adequate liver function: Both Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 3 × ULN (Upper limit of normal), and Serum bilirubin total = 1.5 × ULN (= 3 × ULN for patients with Gilbert's syndrome); 10. Coagulation: Both Activated partial thromboplastin time (APTT) and Pro-thrombin time (PT) = 1.5 × ULN; 11. Patients with the capability to understand and voluntarily sign the written informed consent form, and with the willingness to comply with procedures specified in the protocol. 12. Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 6 months after discontinuing study drug: • Total sexual abstinence is the preferred lifestyle; periodic abstinence is not acceptable; • Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy; • IUDs, • Double-barrier method (contraceptive sponge, diaphragm, or cervical cap with spermicidal jellies or cream, and a condom); • Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) (Note: If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to study drug administration).
Exclusion criteria
Exclusion criteria: Patients that meet any of the following conditions shall not be included in this clinical study: 1. Prior anti-tumor treatments received by patients meet one of the following conditions: a. Use of other cytotoxic agents, other study drugs, or other types of anti-tumor agents within 14 days or 5 half-lives prior to the first dose of study drug (whichever is shorter); b. Use of major surgery within 4 weeks prior to prior to the first dose of study drug or incomplete recovery from the previous surgery (Note: in China, the definition of major surgery refers to the Level 3 and 4 operations specified in the "Administrative Measures for the Clinical Application of Medical Technology" implemented on May 1, 2009) c. Use of systemic radiotherapy within 28 days prior to the first dose of study drug; d. Use of anti-tumor monoclonal antibody therapy within 4 weeks prior to the first dose of study drug; e. Use of steroids for anti-tumor treatment within 7 days prior to the first dose of study drug; f. Unrecovered toxicity(s) from prior anti-tumor therapy (= NCI-CTCAE [version 5.0] Grade 2), except for alopecia; 2. Previous use of allogeneic stem cell transplantation, or use autologous stem cell transplantation within 3 months prior to the first dose of study drug; 3. Central nervous system involvement by lymphoma; 4. Previous use of another BCL-2 family protein inhibitor; 5. Cardiac function and diseases that meet one of the following conditions: a. History of clinically significant QTc interval prolongation, or QTc interval > 470 ms for females and > 450 ms for males at Screening; b. Congestive heart failure = NYHA 2 (New York Heart Association classification); c. Unstable angina, myocardial infarction, or cardiac arrhythmia requiring treatment at Screening; primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); 6. Significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, can adversely affect his/her participation in this study. 7. Pregnant or breast-feeding women (females of childbearing potential should be negative in serum pregnancy test within 7 days prior to the first dose of study drug); 8. History of other active malignancies other than lymphoma within the past 3 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal cell carcinoma of the skin, or localized squamous cell carcinoma of the skin; 9. Dysphagia, malabsorption syndrome, or other conditions that preclude the enteral route of administration. 10. With evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled systemic infection (viral, bacterial, or fungal); positive hepatitis B surface antigen or positive hepatitis B virus DNA; patients who test negative for HBsAg, positive for hepatitis B core antibody (HBcAb), but negative for HBV-DNA can be enrolled test, only if patients agree to receive monthly HBV DNA testing during the study treatment and follow-up; positive hepatitis C virus (HCV) antibody or positive HCV RNA; positive human immunodeficiency virus (HIV) antibody; b. With active and uncontrolled autoimmune cytopenias for 2 weeks or longer, including autoimmune hemolytic anaemia (AIHA) and idiopathic thrombocy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate;Safety: Occurrence of DLT during the DLT observation period;Determination of MTD and PR2D of oral FCN-338 monotherapy in patients with B-cell lymphoma; | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Events, AE;Serious adverse events, SAE;Frequency and causes of death events within 30 days after the last medication use;Efficacy endpoint; | — |
Countries
China
Contacts
Public ContactSong Yuqin
Beijing Cancer Hospital
Outcome results
None listed