A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Bisthianostat in Refractory or Recurrent Multiple Myeloma Patients
Overview
- Phase
- Phase 1
- Intervention
- Bisthianostat
- Conditions
- Refractory Multiple Myeloma
- Sponsor
- Shanghai Theorion Pharmaceutical Co Ltd.
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose of Bisthianostat
- Last Updated
- 6 years ago
Overview
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.
Detailed 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.
Investigators
Eligibility Criteria
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 ≤
- •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
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.
Arms & Interventions
100mg Bisthianostat
100mg starting dose taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Intervention: Bisthianostat
200mg Bisthianostat
200mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Intervention: Bisthianostat
400mg Bisthianostat
400mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Intervention: Bisthianostat
600mg Bisthianostat
600mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Intervention: Bisthianostat
Outcomes
Primary Outcomes
Maximum tolerated dose of Bisthianostat
Time Frame: Up to 24 months
To determine the maximum tolerated dose of Bisthianostat in refractory or recurrent multiple myeloma patients.
Treatment-related adverse events considered as dose-limiting toxicity
Time Frame: During the first cycle (4 weeks)
To evaluate the severity of treatment-related AEs considered as dose-limiting toxicity.
Secondary Outcomes
- 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))
- Half life (T1/2)(During the first cycle (4 weeks))
- Time of Peak Concentration (Tmax)(During the first cycle (4 weeks))
- Objective Response Rate(Up to 1 month after last dose)
- Incidence of adverse events related to treatments(Up to 1 month after last dose)
- Incidence of laboratory abnormalities related to treatments(Up to 1 month after last dose)