A Study of HG146 Capsule in Chinese Subjects With Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study is designed to evaluate the tolerability and safety of HG146 capsule in patients with multiple myeloma.

Detailed Description
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This study is mainly designed to evaluate the tolerability and safety of HG146 capsule in patients with multiple myeloma. Secondly, to get pharmacokinetic data and preliminary efficacy of HG146 capsule in human. This study adopts the traditional design of 3 + 3 dose escalation. The starting dose is 5 mg and subsequent dose group is respectively for 10, 15 and 20 mg. For each dosing group, subjects are administered orally HG146 every other day for two weeks, followed by one week of rest with 21-day as one treatment cycle. Patients will be treated for 4 cycles or disease progression or unacceptable toxicities, whichever comes first.

Official Title
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A Phase I Study of Single-centre, Open-label Clinical Trial to Evaluate HG146 Capsule in the Treatment of Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma, Relapsed and Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: HG146


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma requiring systemic therapy (International Myeloma Working Group [IMWG]) and 2 cycles of treatment including proteasome inhibitors and/or immunomodulators. Serum M protein≥ 10.0g / L, or urine M protein ≥ 200mg / 24h. Not suitable for autologous bone marrow transplantation or refuse autologous bone marrow transplantation or relapse after autologous bone marrow transplantation. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2. Expected survival of ≥3 months. Hemoglobin ≥ 80 g/L, Platelet≥75×10^9/L, Absolute Neutrophil Count≧1.0×109/L (1000 cells/mm3), Prothrombin time(PT) and activated partial thromboplastin time ≤ 2 x Upper Limit of Normal (ULN). Bilirubin in serum<1.5*ULN (2.0mg/dL/20mg/L/34.2μmol/L); glutamic-pyruvic transaminase (ALT) and/or Aspartate Aminotransferase (AST)≤3*ULN (upper limit of normal). Normal electrocardiogram, echocardiography and myocardial enzyme spectrumCalibration of blood calcium concentration≤ULN. Men and women, Non-pregnant women who did not consider giving birth during the trial or five years after the end of the trial. The patient is able to swallow the capsule. Patients must provide written consent. Exclusion Criteria: Severe allergies to the study drug or any of its excipients. The possibility of gene toxicity, mutagenesis and teratogenicity. Men and women who did not have sperm or egg cells stored in vitro before the trial and who planned to have children again within five years. Pregnant or lactating women. Perform autologous bone marrow transplantation 3 months before admission. Receive allogeneic bone marrow transplantation. Use HDAC inhibitors before. Two weeks prior to admission, received radiotherapy or bone marrow suppressive chemotherapy or biological treatment. Patients with history of other malignant tumors, except the tumor is in remission and has not been treated for at least 5 years. Patients with dysphagia or oral absorption disorder. The investigators determine the conditions not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Drug: HG146 capsule HG146 capsule is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma. Other Name: HG280146, HG0146, HG280146, HG280146-P1
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HG146 capsule treat multiple myeloma<br>Experimental: 5/10/15/20 mg HG146 capsule 5 mg starting dose taken orally on Day 1, 3, 5, 7, 9, 11, 13 of each cycle, and off drug for 8 days (3 weeks). Intervention: Drug: HG146 capsule | Drug: HG146<br>* HG146 will be administered every other day for 14 days, followed by 1 week off the drug with each treatment cycle of 21-days.<br>* Other names: HG280146, HG0146, HG280146, HG280146-P1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of HG146 | To determine the maximum tolerated dose of HG146 in relapsed and refractory multiple myeloma patients. | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | To determine the Peak Plasma Concentration of HG146. | In cycle 1 (each cycle is 21 days) | 
| Area under the plasma concentration versus time curve (AUC) | To determine the Area under the plasma concentration versus time curve of HG146. | In the middle of cycle 1 (each cycle is 21 days) | 
| Time of Peak Concentration (Tmax) | To determine the time of peak concentration of HG146. | In the middle of cycle 1 (each cycle is 21 days) | 
| Half life (T1/2) | To determine the half-life of HG146. | In the middle of cycle 1 (each cycle is 21 days) | 
| Incidence of adverse events related to treatments | To evaluate the incidence of adverse events that are related to treatments in relapsed and refractory myeloma patients. | Up to 21 days after last dose | 
| Incidence of laboratory abnormalities related to treatments | To evaluate the incidence of laboratory abnormalities that are related to treatments in relapsed and refractory myeloma patients. | Up to 1 month after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDAC inhibitor, Dose escalation, HG146