this is a phase 1 study of mh048 in patients with selected relapsed/refractory b-cell malignancies

Conditions: Relapsed/Refractory B-cell Malignancies

Summary: this is a phase 1 study of mh048 in patients with selected relapsed/refractory b-cell malignancies.

this is an open-label, multi-center phase 1 study of mh048 in patients with selected relapsed/refractory b-cell malignancies. this study includes 2 parts: part a is the dose escalation part of the study, and part b is the dose expansion part of the study. in part a, patients were enrolled using accelerated titration design for the first three single patient cohorts and 3+3 dose escalation design for the rest cohorts. the starting dose of mh048 in soft gel capsule form was 5 mg/day qd. cycle length will be 28 days. in part b, the dose and lymphoma subtypes for expansion phase will depend on the results from part a.

Eligibility criteria:
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 \[β-hcg\] 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.