Back to resultsA Study of HG146 Capsule in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma, Relapsed and Refractory Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HG146
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring HDAC inhibitor, Dose escalation, HG146
Eligibility Criteria
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.
Sites / Locations
- HitGen Inc
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HG146 capsule treat multiple myeloma
Arm Description
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
Outcomes
Primary Outcome Measures
Maximum tolerated dose of HG146
To determine the maximum tolerated dose of HG146 in relapsed and refractory multiple myeloma patients.
Secondary Outcome Measures
Peak Plasma Concentration (Cmax)
To determine the Peak Plasma Concentration of HG146.
Area under the plasma concentration versus time curve (AUC)
To determine the Area under the plasma concentration versus time curve of HG146.
Time of Peak Concentration (Tmax)
To determine the time of peak concentration of HG146.
Half life (T1/2)
To determine the half-life of HG146.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03710915
Brief Title
A Study of HG146 Capsule in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
Official Title
A Phase I Study of Single-centre, Open-label Clinical Trial to Evaluate HG146 Capsule in the Treatment of Relapsed and Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Company decision
Study Start Date
January 12, 2019 (Actual)
Primary Completion Date
September 28, 2022 (Actual)
Study Completion Date
June 28, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HitGen Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is designed to evaluate the tolerability and safety of HG146 capsule in patients with multiple myeloma.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Relapsed and Refractory Multiple Myeloma
Keywords
HDAC inhibitor, Dose escalation, HG146
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HG146 capsule treat multiple myeloma
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
HG146
Other Intervention Name(s)
HG280146, HG0146, HG280146, HG280146-P1
Intervention Description
HG146 will be administered every other day for 14 days, followed by 1 week off the drug with each treatment cycle of 21-days.
Primary Outcome Measure Information:
Title
Maximum tolerated dose of HG146
Description
To determine the maximum tolerated dose of HG146 in relapsed and refractory multiple myeloma patients.
Time Frame
Up to 3 months
Secondary Outcome Measure Information:
Title
Peak Plasma Concentration (Cmax)
Description
To determine the Peak Plasma Concentration of HG146.
Time Frame
In cycle 1 (each cycle is 21 days)
Title
Area under the plasma concentration versus time curve (AUC)
Description
To determine the Area under the plasma concentration versus time curve of HG146.
Time Frame
In the middle of cycle 1 (each cycle is 21 days)
Title
Time of Peak Concentration (Tmax)
Description
To determine the time of peak concentration of HG146.
Time Frame
In the middle of cycle 1 (each cycle is 21 days)
Title
Half life (T1/2)
Description
To determine the half-life of HG146.
Time Frame
In the middle of cycle 1 (each cycle is 21 days)
Title
Incidence of adverse events related to treatments
Description
To evaluate the incidence of adverse events that are related to treatments in relapsed and refractory myeloma patients.
Time Frame
Up to 21 days after last dose
Title
Incidence of laboratory abnormalities related to treatments
Description
To evaluate the incidence of laboratory abnormalities that are related to treatments in relapsed and refractory myeloma patients.
Time Frame
Up to 1 month after last dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ting Liu, M.D.
Organizational Affiliation
The West China Hospital of Sichuan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
HitGen Inc
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610200
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27881052
Citation
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Results Reference
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PubMed Identifier
25127393
Citation
Lu J, Lu J, Chen W, Huo Y, Huang X, Hou J; Chinese Medical Doctor Association Hematology Branch. Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J. 2014 Aug 15;4(8):e239. doi: 10.1038/bcj.2014.55.
Results Reference
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PubMed Identifier
25439696
Citation
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26.
Results Reference
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PubMed Identifier
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Citation
Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. doi: 10.1002/1097-0142(197509)36:33.0.co;2-u.
Results Reference
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PubMed Identifier
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Citation
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. doi: 10.1200/JCO.2015.61.2267. Epub 2015 Aug 3.
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Citation
Lu J, Lee JH, Huang SY, Qiu L, Lee JJ, Liu T, Yoon SS, Kim K, Shen ZX, Eom HS, Chen WM, Min CK, Kim HJ, Lee JO, Kwak JY, Yiu W, Chen G, Ervin-Haynes A, Hulin C, Facon T. Continuous treatment with lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma in Asia: subanalysis of the FIRST trial. Br J Haematol. 2017 Mar;176(5):743-749. doi: 10.1111/bjh.14465. Epub 2017 Jan 20.
Results Reference
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A Study of HG146 Capsule in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
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