Relapsed/Refractory B-cell MalignanciesPhase 1NCT04689308
This is a Phase 1 Study of MH048 in Patients With Selected Relapsed/Refractory B-cell Malignancies
A Phase 1 study testing MH048 in people with Relapsed/Refractory B-cell Malignancies, run by Minghui Pharmaceutical (Shanghai) LTD at 1 site in China.
Trial summary
This is a Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory B-cell Malignancies
- What is being tested?
- MH048
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteChina
- Study dates
- 7 Jan 2021to 1 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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);
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- 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；
- Medical history of massive bleeding (hemophilia or other disease need the treatment of blood transfusion）;
- Severe neurological/mental illness, and in the opinion of the Investigator, is unable to adhere to the requirements of the study;
- Receipt of any investigational agent or clinical study within 28 days;
- Unstable brain metastasis patient.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the First Affiliated Hospita，Medicine School of Zhejiang University
Hangzhou, Zhejiang, 310003
Jie Jin, M.D., +86-0571-87236114, jiej0503@163.com
About this study
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.
Read the 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
- Being tested
- MH048
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MH048Drug
Also called MH048 Soft Gel Capsules
Soft gel capsules 5 mg and 25 mg，oral MH048 should be administered after an overnight fast.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: MH048 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: Up to approximately 24 Months
Secondary outcomes (6)
Characterization of Pharmacokinetics (Cmax)
Maximum drug concentration (Cmax)
Measured: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (AUC)
Area Under the Curve (AUC)
Measured: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (CL)
Clearance (CL)
Measured: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (t1/2)
Elimination half-life (t1/2)
Measured: At the end of Cycle 1 (each cycle is 28 days)
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.
Measured: From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2020
- Study start7 Jan 2021
- Primary completion30 Jun 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory B-cell MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 57 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Minghui Pharmaceutical (Shanghai) LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jie Jin, MD, Principal investigator, 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04689308
- Sponsor's protocol ID
- MH048-CP001CN
- Status last verified
- Aug 2021
- First submitted
- 14 Dec 2020
- Last updated
- 8 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04689308
- Acronym / sponsor ID
- MH048-CP001CN
- Conditions
- Relapsed/Refractory B-cell Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 57 participants (estimated)
- Lead sponsor
- Minghui Pharmaceutical (Shanghai) LTDIndustry (pharma, biotech, devices)
- Study start
- 7 Jan 2021 (actual)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 30 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Dose Escalation and Determination of RP2D | Experimental | Drug: MH048Part A: Dose Escalation and determination of RP2D, multiple dose levels of MH048 to be evaluated |
| Part B: Dose Expansion in Selected Relapsed/Refractory B-cell Malignancies | Experimental | Drug: MH048Part B: Selected relapsed/refractory B-NHL subjects with at least 1 prior systemic OR standard-of-care therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MH048Also: MH048 Soft Gel CapsulesSoft gel capsules 5 mg and 25 mg，oral MH048 should be administered after an overnight fast. | Drug | Part A: Dose Escalation and Determination of RP2D, Part B: Dose Expansion in Selected Relapsed/Refractory B-cell Malignancies |
Primary outcome
To evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Up to approximately 24 Months
Assess incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0
To determine the MTD of MH048
Time frame: At the end of Cycle 1( 28 day) of each dose escalation cohort.
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.
To establish the RP2D.
Time frame: Up to approximately 24 Months
The determination of RP2D for phase 2 according to the result of dose expansion cohorts.
6 secondary outcomes
Characterization of Pharmacokinetics (Cmax)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (AUC)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (CL)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (t1/2)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR)
Time frame: From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months.
Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR)
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jie Jin, MD principal investigator
79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MH048 in people with Relapsed/Refractory B-cell Malignancies, run by Minghui Pharmaceutical (Shanghai) LTD at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jie Jin, MD (+86 057187236114, jiej0503@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: Up to approximately 24 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2021.