Chronic Lymphocytic Leukemia (CLL), Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Relapsed or Refractory B-cell Lymphoma, Small Lymphocytic Lymphoma (SLL)
Conditions
Brief summary
This is a Phase I/II, single-arm, multicenter, open-label study which is divided into two portions: Phase I is dose escalation portion, in which subjects with relapsed or refractory B-cell lymphoma will be enrolled except malignant lymphoblastic lymphoma (LBL) and Burkitt lymphoma. After the RP2D is identified, Phase II of subjects with relapsed or refractory mantle cell lymphoma who previously received ≥ 2 and ≤ 4 different chemotherapy and/or targeted drug therapy will be enrolled.
Interventions
DRUGMS-553
MS-553 oral tablet BID x 28-days
Sponsors
Shenzhen MingSight Relin Pharmaceutical Co., Ltd
MingSight Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\) Patients in Phase I study will be enrolled with refractory or relapsed B-cell non-Hodgkin lymphoma. * 2\) Patients enrolled in the phase I study failed two or more lines of treatment regimens; Patients with mantle cell lymphoma should also be patients with contraindications or failure of BTK inhibitor therapy. * 3\) Eastern Cooperative Oncology Group (ECOG) performance status score is 0\ 2. * 4\) Have life expectancy ≥ 3 months. * 5\) Major organ functions meet the following criteria: * In the absence of growth factor support therapy or blood transfusion in the last 14 days: absolute neutrophil count ≥1.5×109/L, hemoglobin ≥80 g/L, platelets ≥75×109/L (no platelet transfusion within 14 days); if accompanied with bone marrow invasion, neutrophils ≥1.0×109/L, platelets ≥50×109/L. * Biochemistry: Total bilirubin ≤1.5×ULN or ≤3.0×ULN in Gilbert's syndrome, AST or ALT ≤2.5×ULN, serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault formula). * Coagulation function: International normalized ratio (INR) and activated partial thrombin time ≤ 1.5 × ULN.
Exclusion criteria
* 1\) Present or prior history of other malignancies (except cured carcinoma in situ of cervix and basal cell carcinoma of skin), unless there is radical treatment and no evidence of recurrence or metastasis within the last 2 years. * 2\) Lymphomas involved the central nervous system. * 3\) Patients with history of organ transplantation or allogeneic hematopoietic stem cell transplantation; patients who have received autologous hematopoietic stem cell transplantation or CAR-T treatment within the past 3 months, * 4\) Patients who are suitable and ready for autologous stem cell transplantation. * 5\) History of eye surgery or trauma within 3 months before the screening visit, history of serious eye infection or the most recent eye surgery within 4 weeks before the screening visit. * 6\) Has had active and uncontrolled autoimmune hemocytopenia, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura. * 7\) Has had uncontrolled or significant cardiovascular diseases, including: * 8\) Women who are lactating or pregnant. * 9\) Women of child-bearing potential who do not agree to have two pregnancy tests prior to first dose (at least one of tests is serum pregnancy test) and the test result shall be negative. * 10\) Male patients who do not agree to the birth control measures. * 11\) Any conditions that in the opinion of the investigator considers inappropriate to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicity (DLT) | First cycle (28 days) |
| Incidence and severity of adverse events | up to 24 months |
| To determine the MTD and RP2D of oral MS-553 in patients with BCL | about 8 months |
Secondary
| Measure | Time frame |
|---|---|
| overall survival (OS) | up to 24 months |
| time to progression (TTR) | up to 24 months |
| disease control rate (DCR) | up to 24 months |
| Pharmacokinetics parameters: Cmax | within the first 2 cycles (56 days) |
| Objective response rate (ORR) | up to 24 months |
| Pharmacokinetics parameters: T1/2 | within the first 2 cycles (56 days) |
| Pharmacokinetics parameters: AUC0-12 | within the first 2 cycles (56 days) |
| Pharmacokinetics parameters: CL/F | within the first 2 cycles (56 days) |
| Pharmacokinetics parameters: Tmax | within the first 2 cycles (56 days) |
| Duration of response (DOR) | up to 24 months |
| progression-free survival (PFS) | up to 24 months |
Countries
China
Outcome results
None listed