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

Shanghai Theorion Pharmaceutical

Status and phase: Unknown; Phase 1

Conditions: Refractory Multiple Myeloma; Recurrent Multiple Myeloma

Treatments: Drug: Bisthianostat

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03618602

CH-020PI

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 4 patient groups

100mg Bisthianostat

Experimental group

Description:

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

Treatment:

Drug: Bisthianostat

200mg Bisthianostat

Experimental group

Description:

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

Treatment:

Drug: Bisthianostat

400mg Bisthianostat

Experimental group

Description:

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

Treatment:

Drug: Bisthianostat

600mg Bisthianostat

Experimental group

Description:

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

Treatment:

Drug: Bisthianostat