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

NCT ID: NCT04689308

Last Updated: 2021-09-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-07
• Study Completion Date: 2023-10-01

Brief Summary

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

Detailed Description

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.

Conditions

Relapsed/Refractory B-cell Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Dose Escalation and Determination of RP2D

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

Group Type: EXPERIMENTAL

MH048

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

MH048

Intervention Type: DRUG

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

Interventions

MH048

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

Intervention Type: DRUG

Other Intervention Names

MH048 Soft Gel Capsules

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Minghui Pharmaceutical (Shanghai) LTD

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jie Jin, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

the First Affiliated Hospita，Medicine School of Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jie Jin, MD

Role: CONTACT

jiej0503@163.com

+86 057187236114

Facility Contacts

Jie Jin, M.D.

Role: primary

jiej0503@163.com

+86-0571-87236114

Other Identifiers

MH048-CP001CN

Identifier Type: -

Identifier Source: org_study_id