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

Refractory Multiple Myeloma Clinical Trial

Official title:

A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Bisthianostat in Refractory or Recurrent Multiple Myeloma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03618602
• Other study ID #: CH-020PI
• Status: Recruiting
• Phase: Phase 1
• Start date: April 25, 2018
• Est. completion date: July 2020

Study information

• Verified date: September 2019
• Source: Shanghai Theorion Pharmaceutical Co Ltd.
• Contact: Jian Hou, MD
• Phone: 00862168383144
• Email: houjian[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a first-in-human, single center, open-label, single arm, dose escalating phase I study. This study will be conducted in 3 parts.

Phase A : Patients will receive single dose of bisthianostat to evaluate the single-dose pharmacokinetics and safety.

Phase B: After single-dose phase, patients will receive multiple dose bisthianostat for 4 weeks on day 1,4,11,14,18,21,25,28 to evaluate the multiple-dose pharmacokinetics and safety

Phase C: Patients will continue on the study if they benefit from the drug and not experience any serious side effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• Active infection (Bacteria, fungi, virus etc), fever with body temperature > 38 ? for reasons unknown.

• Other situations that investigator considers it's inappropriate for patients to participate in this study.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

Intervention

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

Locations

Country	Name	City	State
China	Renji Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Theorion Pharmaceutical Co Ltd.	Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of Bisthianostat	To determine the maximum tolerated dose of Bisthianostat in refractory or recurrent multiple myeloma patients.	Up to 24 months
Primary	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	Peak Plasma Concentration (Cmax)	To determine the Peak Plasma Concentration of Bisthianostat.	During the first cycle (4 weeks)
Secondary	Area under the plasma concentration versus time curve (AUC)	To determine the Area under the plasma concentration versus time curve of Bisthianostat.	During the first cycle (4 weeks)
Secondary	Time of Peak Concentration (Tmax)	To determine the time of peak concentration of Bisthianostat.	During the first cycle (4 weeks)
Secondary	Half life (T1/2)	To determine the half-life of Bisthianostat.	During the first cycle (4 weeks)
Secondary	Objective Response Rate	To evaluate the objective response rate in refractory or recurrent myeloma patients after bisthianostat treatments.	Up to 1 month after last dose
Secondary	Incidence of adverse events related to treatments	To evaluate the incidence of adverse events that are related to treatments in refractory or recurrent myeloma patients	Up to 1 month after last dose
Secondary	Incidence of laboratory abnormalities related to treatments	To evaluate the incidence of laboratory abnormalities that are related to treatments in refractory or recurrent myeloma patients	Up to 1 month after last dose