Safety, Pharmacokinetics and Efficacy Study of Bisthianostat in Refractory or Recurrent Multiple Myeloma Patients

NCT03618602 | Unknown Phase 1

• 1 other identifier: CH-020PI
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human study to investigate the safety, tolerability, pharmacokinetics, and efficacy of Bisthianostat in refractory or recurrent multiple myeloma patients.

Conditions

Refractory Multiple Myeloma; Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of Bisthianostat

  To determine the maximum tolerated dose of Bisthianostat in refractory or recurrent multiple myeloma patients.

  Up to 24 months

• Treatment-related adverse events considered as dose-limiting toxicity

  To evaluate the severity of treatment-related AEs considered as dose-limiting toxicity.

  During the first cycle (4 weeks)

Secondary Outcomes (7)

• Peak Plasma Concentration (Cmax)

  During the first cycle (4 weeks)

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

  During the first cycle (4 weeks)

• Time of Peak Concentration (Tmax)

  During the first cycle (4 weeks)

• Half life (T1/2)

  During the first cycle (4 weeks)

• Objective Response Rate

  Up to 1 month after last dose

Study Arms (4)

100mg Bisthianostat

EXPERIMENTAL

100mg starting dose taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).

Drug: Bisthianostat

200mg Bisthianostat

EXPERIMENTAL

200mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).

Drug: Bisthianostat

400mg Bisthianostat

EXPERIMENTAL

400mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).

Drug: Bisthianostat

600mg Bisthianostat

EXPERIMENTAL

600mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).

Drug: Bisthianostat

Interventions

Bisthianostat DRUG

Bisthianostat is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma.

Also known as: CF367-C, CFH367-C, CF367, PY-1

100mg Bisthianostat; 200mg Bisthianostat; 400mg Bisthianostat; 600mg Bisthianostat

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed as stage II or III (Durie-Salmon Staging System) multiple myeloma with disease progression or recurrence after at least two cycles of systemic antimyeloma treatment.
• Serum M protein≥ 5.0g / L, or urine M protein ≥ 200mg / 24h, or serum free light chain ≥ 200mg / L.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Expected survival of ≥3 months.
• Female participants of childbearing potential should have negative urine pregnancy test in screening period (accept previous test result within 14 days before screening), and must agree to adopt effective contraceptive measures within 14 days before receiving first dose of study drug, during the treatment period and within 28 days after final dose of study drug.
• Male participants must agree to adopt effective contraceptive measures and not allowed to donate sperms during the treatment period, and within 28 days after final dose of study drug.
• Hemoglobin ≥ 80 g/L, Platelet≥50×109/L (50,000/mm3), 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)
• AST or ALT ≤ 1.5 x ULN, total bilirubin≤ 1.5 x ULN;
• Serum Creatinine ≤ 1.5 x ULN, glomerular filtration rate≥ 50 ml/min;
• NYHA Class I or II
• Written informed consent obtained prior to participation in the study

You may not qualify if:

• Pregnant or lactating women.
• Non-secretory multiple myeloma patients.
• Plasma cell leukemia patients.
• Received any anti-cancer medication or experimental drugs against multiple myeloma within 1 week before first dose of bisthianostat, any experimental treatment other than medication (eg. leukocyte donor/monocyte infusion) within 56 days before first dose of bisthianostat. Participation in any other drug or medical devices within 56 days before the study.
• Stem cell transplant planned on the following 28 days.
• Uncontrolled hypercalcemia after treatments, eg. saline infusion.
• Renal insufficiency required hemodialysis or peritoneal dialysis.
• NCI-CTCAE grade 2 Peripheral Neuropathy.
• Serious heart disease in the past 6 months, including angina requiring surgery, uncontrolled hypertension after anti-hypertensive treatments (Systolic blood pressure\> 160 mmHg, Diastolic blood pressure\>90mmHg); Myocardial infarction; Grade II-IV congestive heart failure; unstable angina.
• HIV, HCV or HBV (HBV-DNA \> 20 IU/mL) infection.
• Patients with any other prior malignancy, except for skin basal cell carcinoma, cervical carcinoma in situ, breast carcinoma in situ, skin squamous cell carcinoma that have been treated and controlled.
• Imaging evidences show tumors have involved main blood vessels and nerves.
• Patients with significant central nervous system lesions.
• Patients with mental illness.
• Patients with history of alcohol or drug abuse, patients with allergy to the active ingredient or excipients of study drug, and patients who are unable or unwilling to receive the intravenous administration.

Sponsors & Collaborators

• Shanghai Theorion Pharmaceutical Co Ltd.: lead
• Shanghai Institute of Materia Medica, Chinese Academy of Sciences: collaborator

Study Sites (1)

Renji Hospital

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Jian Hou, MD

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Hou, MD

CONTACT

00862168383144; houjian@medmail.com.cn

Honghui Huang, MD

CONTACT

00862168383144; honghui_huang@163.com

Study Design

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

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 7, 2018
• Study Start: April 25, 2018
• Primary Completion: April 1, 2020
• Study Completion: July 1, 2020
• Last Updated: September 19, 2019

Record last verified: 2019-09

Locations

CN (1)