This is a Phase 1 Study of MH048 in Patients With Selected Relapsed/Refractory B-cell Malignancies

NCT04689308 | Unknown Phase 1

• 1 other identifier: MH048-CP001CN
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies.

Conditions

Relapsed/Refractory B-cell Malignancies

Outcome Measures

Primary Outcomes (3)

• 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

• 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.

• 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 Outcomes (6)

• Characterization of Pharmacokinetics (Cmax)

  At the end of Cycle 1 (each cycle is 28 days)

• Characterization of Pharmacokinetics (AUC)

  At the end of Cycle 1 (each cycle is 28 days)

• Characterization of Pharmacokinetics (CL)

  At the end of Cycle 1 (each cycle is 28 days)

• Characterization of Pharmacokinetics (t1/2)

  At the end of Cycle 1 (each cycle is 28 days)

• Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR)

  From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months.

Study Arms (2)

Part A: Dose Escalation and Determination of RP2D

EXPERIMENTAL

Part A: Dose Escalation and determination of RP2D, multiple dose levels of MH048 to be evaluated

Drug: MH048

Part B: Dose Expansion in Selected Relapsed/Refractory B-cell Malignancies

EXPERIMENTAL

Part B: Selected relapsed/refractory B-NHL subjects with at least 1 prior systemic OR standard-of-care therapy.

Drug: MH048

Interventions

MH048 DRUG

Soft gel capsules 5 mg and 25 mg，oral MH048 should be administered after an overnight fast.

Also known as: MH048 Soft Gel Capsules

Part A: Dose Escalation and Determination of RP2D; Part B: Dose Expansion in Selected Relapsed/Refractory B-cell Malignancies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ≥18 years of age;
• Willing and able to understand and sign an informed consent form and to comply with all aspects of the protocol;
• Life expectancy of ≥12 weeks;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
• 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;
• There must be radiographically measurable disease for effects assess at dose expansion cohort;
• 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 );
• Willing to have bone marrow biopsy/aspirate for baseline disease assessment and assessment of response to treatment;
• 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.

You may not qualify if:

• 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;
• 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;
• 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;
• Transformation (e.g., Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma) prior to the planned start of MH048 treatment;
• Subjects with known or suspected history of allergy to MH048 capsules or excipients;
• 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);
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection;
• Active uncontrolled autoimmune disease;
• Clinically significant active malabsorption syndrome;
• 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);
• Major surgery within 4 weeks prior to planned start of MH048 treatment (expect for biopsy, laser eye surgery)；
• Women of childbearing potential who are pregnant or lactating;
• Subjects requiring therapeutic anticoagulation;
• Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of MH048 treatment;
• Received a CYP3A4, CYP2A8 strong inhibitor or inducer within 5 half-lives of planned investigational product administration；

Sponsors & Collaborators

• Minghui Pharmaceutical (Shanghai) LTD: lead

Study Sites (1)

the First Affiliated Hospita，Medicine School of Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jie Jin, MD

  79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Jin, MD

CONTACT

+86 057187236114; jiej0503@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 30, 2020
• Study Start: January 7, 2021
• Primary Completion: June 30, 2023
• Study Completion: October 1, 2023
• Last Updated: September 8, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)