B-cell lymphoma
Conditions
Interventions
dose escalation:HBW-3210 capule
dose expansion:HBW-3210 capule
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1) Aged 18 to 80 years old, male and female. 2) Primary Central Nervous System Lymphoma: KPS score >= 60; Other lymphomas: Eastern Cooperative Oncology Group (ECOG) Physical Status Score of 0~2. (Dose Escalation Phase: ECOG Physical Status Score of 0~1). 3)Expected survival of more than 3 months as judged by the investigator. 4)Recurrent/refractory B-cell non Hodgkin's lymphoma confirmed by histopathology and/or cytology, who has received at least one standardized treatment in the past. This includes Primary central nervous system lymphoma (PCNSL) or Secondary central nervous system lymphoma (SCNSL), Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphomas (MCL), Follicular lymphoma (FL), Marginal zone lymphoma (MZL), Waldenström's macroglobulinemia (WM)/ Lymphoplasmacytic Lymphoma (LPL), and Diffuse large B cell lymphoma (DLBCL). The definition of recurrence is: the disease progresses after the patient reaches Complete remission (CR) or Partial remission (PR) and the remission lasts for >= 6 months; Difficult to treat is defined as: ineffective treatment (without obtaining CR and PR), or disease progression occurring during the treatment period or remission lasting for less than 6 months. For Mantle cell lymphoma (MCL) and Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL), previous treatment needs to include a BTK inhibitor and immunochemotherapy, or treatment regimens containing an anti-CD20 monoclonal antibody is not suitable after treatment failure, recurrence, or intolerance with BTK inhibitors. 5)Any non-hematological toxicity related to previous treatment should be restored to level 1 or normal (excluding hair loss according to NCI CTCAE 5.0). 6)Have measurable lesions or efficacy evaluation indicators: For patients with central nervous system involvement, it is required to display substantial lesions (>10 * 10mm) of disease progression on contrast-enhanced MRI; Only patients with brain lesions require cytological examination of cerebrospinal fluid (CSF) to confirm lymphoma cells and/or imaging findings consistent with CSF examination; For CLL and WM/LPL patients, when baseline imaging evaluation determines the absence of two-dimensional measurable lesions, treatment indications and evaluable indicators must be present. As follows: For CLL, peripheral blood monoclonal B lymphocytes >= 5.0×10^9/L; For WM, IgM>1.5×ULN; For LPL, IgM or other immunoglobulins>1.5 × ULN; For other B-NHL, there should be at least one two-dimensional measurable lesion confirmed by imaging (CT or MRI) (any length diameter of lymph node lesion>1.5cm or any length diameter of extranodal lesion>1.0cm). 7)The main organ functions meet the following standards: a. Blood routine test without growth factor support treatment or blood transfusion within 7 days: Absolute neutrophil count >= 1.0 × 10^9/L, Platelet count >= 75 × 10^9/L, hemoglobin >= 80g/L; b. Liver function: serum total bilirubin = 60mL/min. The calculation formula is eGFR=a × (Scr/b) c × (0.993) Age; d. Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time <= 1.5 × ULN. 8) Be able to swallow capsules and comply with outpatient treatmen
Exclusion criteria
Exclusion criteria: 1) PCNSL pathological classification includes immunodeficiency associated lymphoma, intravascular large B-cell lymphoma, Burkitt lymphoma, T-cell lymphoma, and NK/T-cell lymphoma. 2) Presence vitreoretinal lymphoma. 3) Have received any of the following treatments in the past: a. Received non-targeted small molecule chemotherapy, large molecule targeted anti-tumor therapy, or anti-tumor immunotherapy (including clinical trial drugs) within 4 weeks before the first administration of the study drug; b. Received small molecule targeted anti-tumor drug therapy (including clinical trial drugs, with a washout period of no less than 7 days) within the first 5 half-lives of the study drug administration; c. Within 4 weeks prior to the first administration of the investigational drug, pelvic, cranial, or sternal region (containing bone marrow) radiotherapy or whole brain radiotherapy; Palliative radiation therapy for other locally irradiated areas within one week; d. Within 2 weeks prior to the first administration of the study drug, traditional Chinese medicine with clear anti-tumor effects were received for treatment; e. Within 2 weeks prior to the first administration of the investigational drug, steroid hormone anti-tumor therapy was received with a dosage that meets the following conditions: for the treatment of non-tumor diseases, a dosage greater than 2.25mg/d dexamethasone or equivalent; If treating tumor diseases, use a dose of>5mg/d dexamethasone or equivalent dose; f. Experimental drug treatment with an unknown half-life within 4 weeks prior to the first administration of the study drug. 4) Vaccine used within 4 weeks prior to the first administration of the study drug 5) Plan to use other systemic anti-cancer treatments simultaneously during the study period 6) Within 4 weeks before the first administration of the study drug or during the study period, anticoagulant therapy such as warfarin or vitamin K antagonists is required, or there is a tendency for bleeding or coagulation disorders 7) Strong CYP3A4 inhibitor or inducer have been taken within 2 weeks prior to the first administration of the study drug 8) Major surgery (excluding vascular catheterization, biopsy, or laser ophthalmic surgery) performed within 28 days prior to the first administration of the study drug 9) Received allogeneic or autologous Stem cell transplantation (SCT) or Chimeric antigen receptor T cells (CAR-T) treatment within 6 months prior to the first administration of the study drug 10) Suffering from poorly controlled active autoimmune hemocytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]), which requiring initiation of new therapy or increasing the dose of pre-existing therapy to maintain adequate blood counts within 28 days prior to enrollment in the study 11) Suffering from significant cardiovascular diseases within 12 months prior to the first administration of the study drug, such as: a. unstable angina; b. Occurrence of myocardial infarction; c. Left ventricular ejection fraction (LVEF) 159mmHg or diastolic blood pressure>99mmHg) 12) During the screening period, at least 2 out of 3 consecutive electrocardiogram (ECG) recordings showed an extended QT interva
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose,MTD;Dose-limiting toxicity,DLT;Overall Response Rate,ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response,DOR;Time to response,TTR;Progression-free survival,PFS;Overall survival,OS;Partical Response,PR;Complete response,CR;Disease control rate,DCR;Tmax;Cmax;t1/2;CL/F;Vd/F;AUC; | — |
Countries
China
Contacts
Public ContactWenbin Li
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed