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

NCT03710915 | Terminated Phase 1

• 1 other identifier: HG146-I-CRP-1.0
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma; Relapsed and Refractory Multiple Myeloma

Keywords

HDAC inhibitor; Dose escalation; HG146

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Peak Plasma Concentration (Cmax)

  In cycle 1 (each cycle is 21 days)

• Area under the plasma concentration versus time curve (AUC)

  In the middle of cycle 1 (each cycle is 21 days)

• Time of Peak Concentration (Tmax)

  In the middle of cycle 1 (each cycle is 21 days)

• Half life (T1/2)

  In the middle of cycle 1 (each cycle is 21 days)

• Incidence of adverse events related to treatments

  Up to 21 days after last dose

Study Arms (1)

HG146 capsule treat multiple myeloma

EXPERIMENTAL

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

Interventions

HG146 DRUG

HG146 will be administered every other day for 14 days, followed by 1 week off the drug with each treatment cycle of 21-days.

Also known as: HG280146, HG0146, HG280146, HG280146-P1

HG146 capsule treat multiple myeloma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HitGen Inc.: lead

Study Sites (1)

HitGen Inc

Chengdu, Sichuan, 610200, China

Location

Related Publications (6)

• Huang B, Lu J, Wang X, Xiao Y, Zhao Y, Huang H, Liu J, Chen M, Gu J, Yuan S, Zheng D, Li Y, Huang X, Li J. Prognostic value of lactate dehydrogenase in Chinese patients with newly diagnosed transplant eligible multiple myeloma. Leuk Lymphoma. 2017 Jul;58(7):1740-1742. doi: 10.1080/10428194.2016.1252975. Epub 2016 Nov 23. No abstract available.

  PMID: 27881052 BACKGROUND

• 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.

  PMID: 25127393 BACKGROUND

• 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.

  PMID: 25439696 BACKGROUND

• 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.

  PMID: 1182674 BACKGROUND

• 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.

  PMID: 26240224 BACKGROUND

• 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.

  PMID: 28106903 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ting Liu, M.D.

  The West China Hospital of Sichuan University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 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

Study Record Dates

• First Submitted: September 29, 2018
• First Posted: October 18, 2018
• Study Start: January 12, 2019
• Primary Completion: September 28, 2022
• Study Completion: June 28, 2023
• Last Updated: October 10, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)