Relapsed/Refractory B-cell Malignancies Clinical Trial
Official title:
A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Antitumor Activity of MH048 in Subjects With Selected Relapsed/Refractory B-cell Malignancies
This is a Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies.
Status | Recruiting |
Enrollment | 57 |
Est. completion date | October 1, 2023 |
Est. primary completion date | June 30, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Male or female subjects =18 years of age; 2. Willing and able to understand and sign an informed consent form and to comply with all aspects of the protocol; 3. Life expectancy of =12 weeks; 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2; 5. Histologically confirmed B-cell Malignancies who have relapsed or are refractory to standard of care therapies, and have received =1 prior lines of therapy: Part A: Subjects with B-cell Malignancies (regardless of subtype); Part B: Subjects With Selected Relapsed/Refractory B-cell Malignancies based on data from Part A; 6. There must be radiographically measurable disease for effects assess at dose expansion cohort; 7. Adequate organ function, as specified below: Hematologic: Platelet count >65 × 10^9/L (may be posttransfusion, must one week before the first dose of starting study treatment); Hemoglobin (Hgb) = 80 g/L; international normalized ratio (INR) or plasma prothrombin time (PT) =1.5 × ULN; absolute neutrophil count >1.0 × 10^9/L (growth factor use is allowed to bring pre-treatment neutrophils to >1.0 × 10^9 cells/L if bone marrow infiltration is involved, provided this is not within 7 days of starting study treatment); Hepatic: Total bilirubin <1.5 × upper limit normal (ULN), Total bilirubin <3 × ULN for Gilbert Syndrome; Aspartate aminotransferase (AST) and Alanine transaminase (ALT) =2.5 × ULN; Renal: Creatinine clearance =60 mL/min (as estimated by the Cockcroft-Gault equation ); 8. Willing to have bone marrow biopsy/aspirate for baseline disease assessment and assessment of response to treatment; 9. Willingness of men and women of reproductive potential to observe conventional and highly effective birth control from the beginning of the study screening until 6 months after receiving the last treatment of investigational product. A fertile woman must be confirmed by a positive serum beta-human chorionic gonadotropin [ß-hCG] test before 7 days of starting study treatment. Exclusion Criteria: 1. History of other active malignancies within 1 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix, localized basal cell or squamous cell carcinoma of skin, previous malignancy that was not recurred in 5 years; 2. History of allogeneic or autologous stem cell transplant or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 100 days before starting study treatment, or diagnosis of graft vs host disease; 3. Clinically significant, uncontrolled cardiac or cardiovascular disease, or history of myocardial infarction, New York Heart Association (NYHA) Class III or IV, QTc prolongation (defined as a QTc > 450 ms) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) ,within 6 months prior to planned start of MH048 treatment; 4. Transformation (e.g., Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma) prior to the planned start of MH048 treatment; 5. Subjects with known or suspected history of allergy to MH048 capsules or excipients; 6. Any unresolved toxicities from prior therapy of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0) Grade 2 or higher at the time of starting MH048 treatment, with the exception of toxicities not considered a safety risk (eg, alopecia, neuropathy, or asymptomatic laboratory abnormalities); 7. Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection; 8. Active uncontrolled autoimmune disease; 9. Clinically significant active malabsorption syndrome; 10. Subjects with human immunodeficiency virus (HIV) , Active hepatitis B virus (HBsAg positive, or HBsAg negative/HBcAb positive ,and HBV DNA>10^3) or Active HCV infection (HCVAb positive ,and HCV RNA positive); 11. Major surgery within 4 weeks prior to planned start of MH048 treatment (expect for biopsy, laser eye surgery); 12. Women of childbearing potential who are pregnant or lactating; 13. Subjects requiring therapeutic anticoagulation; 14. Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of MH048 treatment; 15. Received a CYP3A4, CYP2A8 strong inhibitor or inducer within 5 half-lives of planned investigational product administration; 16. Medical history of massive bleeding (hemophilia or other disease need the treatment of blood transfusion); 17. Severe neurological/mental illness, and in the opinion of the Investigator, is unable to adhere to the requirements of the study; 18. Receipt of any investigational agent or clinical study within 28 days; 19. Unstable brain metastasis patient. |
Country | Name | City | State |
---|---|---|---|
China | the First Affiliated Hospita,Medicine School of Zhejiang University | Hangzhou | Zhejiang |
Lead Sponsor | Collaborator |
---|---|
Minghui Pharmaceutical (Shanghai) LTD |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] | Assess incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0 | Up to approximately 24 Months | |
Primary | To determine the MTD of MH048 | If 2 or more treated subjects at a dose level experience a DLT before Day 28, dose escalation will stop and the prior dose level will be considered the MTD for that schedule. | At the end of Cycle 1( 28 day) of each dose escalation cohort. | |
Primary | To establish the RP2D. | The determination of RP2D for phase 2 according to the result of dose expansion cohorts. | Up to approximately 24 Months | |
Secondary | Characterization of Pharmacokinetics (Cmax) | Maximum drug concentration (Cmax) | At the end of Cycle 1 (each cycle is 28 days) | |
Secondary | Characterization of Pharmacokinetics (AUC) | Area Under the Curve (AUC) | At the end of Cycle 1 (each cycle is 28 days) | |
Secondary | Characterization of Pharmacokinetics (CL) | Clearance (CL) | At the end of Cycle 1 (each cycle is 28 days) | |
Secondary | Characterization of Pharmacokinetics (t1/2) | Elimination half-life (t1/2) | At the end of Cycle 1 (each cycle is 28 days) | |
Secondary | Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR) | The number (%) of subjects with best overall response (BoR) of CR or PR. | From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months. | |
Secondary | Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) | The duration from the first documentation of CR or PR to the first documented PD or death due to any cause, whichever occurs first. | From the first documented of CR or PR to the first documented PD or death due to any cause, whichever came first, , assessed up to approximately 24 months. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
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