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

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ClinicalTrials.gov Identifier: NCT03618602
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Information provided by (Responsible Party):
Shanghai Theorion Pharmaceutical Co Ltd.

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.

Condition or disease Intervention/treatment Phase
Refractory Multiple Myeloma Recurrent Multiple Myeloma Drug: Bisthianostat Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Bisthianostat in Refractory or Recurrent Multiple Myeloma Patients
Actual Study Start Date : April 25, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: 100mg Bisthianostat
100mg starting dose taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Drug: Bisthianostat
Bisthianostat is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma.
Other Name: CF367-C, CFH367-C, CF367, PY-1

Experimental: 200mg Bisthianostat
200mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Drug: Bisthianostat
Bisthianostat is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma.
Other Name: CF367-C, CFH367-C, CF367, PY-1

Experimental: 400mg Bisthianostat
400mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Drug: Bisthianostat
Bisthianostat is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma.
Other Name: CF367-C, CFH367-C, CF367, PY-1

Experimental: 600mg Bisthianostat
600mg Bisthianostat taken orally on Day 1, 4,7,11,14,18,21,25 and 28 of each cycle(4 weeks).
Drug: Bisthianostat
Bisthianostat is a histone deacetylase inhibitor (HDAC inhibitor) for the treatment of multiple myeloma.
Other Name: CF367-C, CFH367-C, CF367, PY-1




Primary Outcome Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. Peak Plasma Concentration (Cmax) [ Time Frame: During the first cycle (4 weeks) ]
    To determine the Peak Plasma Concentration of Bisthianostat.

  2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: During the first cycle (4 weeks) ]
    To determine the Area under the plasma concentration versus time curve of Bisthianostat.

  3. Time of Peak Concentration (Tmax) [ Time Frame: During the first cycle (4 weeks) ]
    To determine the time of peak concentration of Bisthianostat.

  4. Half life (T1/2) [ Time Frame: During the first cycle (4 weeks) ]
    To determine the half-life of Bisthianostat.

  5. Objective Response Rate [ Time Frame: Up to 1 month after last dose ]
    To evaluate the objective response rate in refractory or recurrent myeloma patients after bisthianostat treatments.

  6. Incidence of adverse events related to treatments [ Time Frame: Up to 1 month after last dose ]
    To evaluate the incidence of adverse events that are related to treatments in refractory or recurrent myeloma patients

  7. Incidence of laboratory abnormalities related to treatments [ Time Frame: Up to 1 month after last dose ]
    To evaluate the incidence of laboratory abnormalities that are related to treatments in refractory or recurrent myeloma patients



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≤ 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03618602


Contacts
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Contact: Jian Hou, MD 00862168383144 houjian@medmail.com.cn
Contact: Honghui Huang, MD 00862168383144 honghui_huang@163.com

Locations
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China, Shanghai
Renji Hospital Recruiting
Shanghai, Shanghai, China, 200127
Contact: Hou Jian    00862158752345    hou.jian@renji.com   
Sponsors and Collaborators
Shanghai Theorion Pharmaceutical Co Ltd.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Investigators
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Principal Investigator: Jian Hou, MD RenJi Hospital

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Responsible Party: Shanghai Theorion Pharmaceutical Co Ltd.
ClinicalTrials.gov Identifier: NCT03618602     History of Changes
Other Study ID Numbers: CH-020PI
First Posted: August 7, 2018    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases