Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma, Mantle-Cell, Transformed Follicular Lymphoma (TFL)
Conditions
Brief summary
This is an investigator-initiated, open-label, single-arm, dose-escalation and dose-expansion study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of MTM-H-001 in adult participants with relapsed/refractory (R/R) B-cell malignancies.
Interventions
Each participant receives MTM-H-001 Injection
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
MagicTime Medicine
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged 18 - 75 years old (inclusive); 2. The participant or his/her legally acceptable representative gives consent to this clinical study participation and signs an Informed Consent Form (ICF) indicating their understanding of the objectives and procedures of the clinical study and willingness to participate in the study; 3. Participants with histopathologically and immunohistochemically confirmed Non-Hodgkin B-cell Lymphoma (B-NHL) according to the 2016 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (CLL/SLL diagnosed in accordance with 2018 iwCLL criteria) 4. Relapsed or refractory disease after receiving at least two prior lines of standard therapy, or relapsed or refractory disease after receiving autologous hematopoietic stem cell transplant (ASCT) (if applicable). 5. Adequate major organ function, defined as meeting the following criteria: 1. Hematology: Hemoglobin (Hb) ≥80 g/L; absolute neutrophil count (ANC) ≥1.0×10\^9/L; and platelet count (PLT) ≥75×10\^9/L; 2. Coagulation: International Normalized Ratio (INR) ≤1.5×Upper Limit of Normal (ULN) and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; 3. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0×Upper Limit of Normal (ULN); 4. Serum Total Bilirubin (TBIL) ≤1.5×ULN (except for participants with documented Gilbert's syndrome); 5. Blood creatinine (Cre) ≤1.5×ULN, or calculated creatinine clearance (Ccr) ≥50 mL/min (using the Cockcroft-Gault formula); 6. Cardiac function: Good hemodynamic stability, Left Ventricular Ejection Fraction (LVEF) ≥50%; 6. Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2; 7. Expected survival \>3 months; 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and agree to use at least one effective contraceptive method throughout the study and within 6 months after the last treatment cycle.
Exclusion criteria
1. B-NHL participants with a history of Richter's transformation of chronic lymphocytic leukemia (CLL). 2. Primary central nervous system (CNS) lymphoma, or malignant tumors involving the CNS. 3. Burkitt's lymphoma/leukemia, primary mediastinal large B-cell lymphoma (LBCL). 4. Known history of other malignancies within the past 5 years, excluding cured localized tumors (including cervical carcinoma in situ, basal cell carcinoma of the skin, and prostate carcinoma in situ, etc.); 5. Active hepatitis B virus (HBV) infection; 6. Active hepatitis C virus (HCV) infection; 7. Active human immunodeficiency virus (HIV) infection or a past history of HIV infection; 8. Uncontrolled active infection requiring intravenous treatment within one week prior to the first dose; 9. Corrected QT interval using Fridericia (QTcF) is ≥450 ms (male) or ≥470 ms (female) according to the electrocardiography (ECG) examination results at screening; 10. Currently experiencing or having experienced within the past 6 months any of the following: 1. Congestive heart failure (New York Heart Association \[NYHA\] Class III-IV); 2. Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg with medication treatment; 3. Myocardial infarction, clinically significant arrhythmias, unstable angina, Torsades de Pointes, left bundle branch block or bifascicular block, coronary/peripheral artery bypass grafting, congenital long QT syndrome; 4. Cerebrovascular accident, transient ischaemic attack; 5. Symptomatic pulmonary embolism; 11. History of any mental disorders (e.g., schizophrenia, bipolar disorder, eating disorders, major depression, or anxiety) as reported by the participant or documented in medical records; 12. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | 42 days following first dose of MTM-H-001 for each participant | Percentage of participants experiencing DLTs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Throughout the study, up to 24 months | Percentage of participants who achieve complete response (CR) and partial response (PR) (evaluated by the investigator according to the criteria of Lugano 2014 and iWCLL 2018). |
| Disease control rate (DCR) | Throughout the study, up to 24 months | Percentage of participants who achieve complete response (CR), partial response (PR) and stable disease (SD). |
| Time to response (TTR) | Throughout the study, up to 24 months | Time from the first dose of MTM-H-001 to the first documented response (CR or PR). |
| Duration of response (DOR) | Throughout the study, up to 24 months | Time from the first documented objective response (CR or PR) to the first documented progressive disease (PD) or death from any cause (whichever occurs first). |
| Event-free survival (EFS) | Throughout the study, up to 24 months | Time from the first dose of MTM-H-001 to the first documented PD or relapse, initiation of any new anti-lymphoma treatment, or death from any cause (whichever occurs first). |
| Progression free survival (PFS) | Throughout the study, up to 24 months | Time from the first dose of MTM-H-001 to the first documented PD or death from any cause (whichever occurs first). |
| Overall survival (OS) | Throughout the study, up to 24 months | Time from the first dose of MTM-H-001 to death from any cause. |
Countries
China
Contacts
CONTACTMichael Green
PRINCIPAL_INVESTIGATORNing Li, Ph.D
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed