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Safety and Efficacy Assessments of Osalmid in Multiple Myeloma

Sponsor
Shanghai 10th People's Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03670173
Collaborator
Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Other)
20
Enrollment
1
Location
1
Arm
31.5
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety and efficacy of a traditional cholagogue drug osalmid, 2-hydroxy-N-(4-hydroxyphenyl)-benzamide, in the treatment of multiple myeloma (MM).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Osalmid, 2-hydroxy-N-(4-hydroxyphenyl)-benzamide, is a traditional cholagogue and is clinically used in China to promote biliary drainage and protect liver function. Studies have shown that osalmid is an inhibitor of ribonucleotide reductase (RR). Recently, it was proven by our group that osalmid induced a dose-dependent lethality in multiple myeloma (MM) cell lines H929, OPM2, U266, OCI-MY5, and RPMI 8266, as well as in MM xenograft mouse models. This study aims to assess the safety and efficacy of osalmid in the treatment of MM.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
multi-center, single-arm, open-label, non-blindmulti-center, single-arm, open-label, non-blind
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy Assessments of Osalmid in the Treatment of Multiple Myeloma
Actual Study Start Date :
Oct 1, 2018
Anticipated Primary Completion Date :
May 18, 2021
Anticipated Study Completion Date :
May 18, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Osalmid

Participants are initially given oral capsules with 0.5g tid osalmid daily for two weeks. Thereafter, the dosage will be increased by 0.25g tid every two weeks as tolerated by participants to a maximum daily dosage of 1.0g tid for up to one year. One course of osalmid treatment lasts four weeks. Response will be assessed at the end of each treatment course, and patients who have achieved MR (minor remission) or more than MR at the end of the fourth course will continue to take 1.0g tid osalmid daily for consolidation / maintenance therapy. Otherwise, patients who have not achieved MR at the end of the fourth course and patients who are assessed for PD (progression of disease) at the end of each course will receive salvage treatment, such as a combined treatment of osalmid and dexamethasone or the VCD (bortezomib, cyclophosphamide and dexamethasone) regimen.

Drug: Osalmid
Participants are initially given oral capsules with 0.5g tid osalmid daily for two weeks. Thereafter, the dosage will be increased by 0.25g tid every two weeks as tolerated by participants to a maximum daily dosage of 1.0g tid for up to one year.
Other Names:
  • 2-hydroxy-N-(4-hydroxyphenyl)-benzamide

    		•

    Outcome Measures

    Primary Outcome Measures

    1. overall response rate [at week16]

      M protein qualification in serum and/or urine decline of at least 25%, 50%, 75%, or 90%

    Secondary Outcome Measures

    1. time to progression [at week 48]

      from the start of therapy to disease progression

    2. duration of response [at week 48]

      from the time response was achieved to disease progression or death

    3. progression-free survival [at week 48]

      from study entry to disease progression or death

    4. overall survival [at week 48]

      from the date of study entry to the date of death or last follow-up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients with age≥ 18 years old who are willing to receive the treatment of osalmid;

    2. Patients must be diagnosed with active and measurable (symptomatic) multiple myeloma according to IMWG 2003/WHO 2008(V4) MM diagnosis criteria detailed as following:1). Positive M protein in serum and/or urine; 2). Pathologically diagnosed with multiple myeloma or found colonic plasma cells in bone marrow; 3). At least one symptom of related organ damage or tissue lesion: a. hypercalcemia: serum calcium increases 0.25mmol/L or more over upper limit of normal value(ULN) or > 2.75mmol/L; b. anemia: Hemoglobin decreases 20g/L or more over lower limit of normal value(LLN) or <100g/L；c. bone lesion: lytic bone lesion or osteoporosis accompanied with compressive fracture (confirmed with MRI、CT or PET-CT); d. others: symptomatic hyperviscosity, amyloidosis, recurrent infection (more than twice within 12 months);

    3. Eastern Cancer Organization Group (ECOG) score≤2 and expected survival>2 months;

    4. Belongs to "measurable disease": serum M protein ≥10g/L and/or 24 hour urine M protein ≥200mg;

    5. No active infectious diseases;

    6. No severe organic dysfunction (except renal function insufficiency caused by multiple myeloma), lab results must meet the following criteria (within 7 days before initiation of therapy): a. Total bilirubin ≤ 1.5ULN (same age group); b. AST and ALT ≤ 2.5ULN (same age group); c. Cardiac enzyme < 2*ULN (same age group); d. Normal ejection fraction confirmed in echo;

    7. Able to swallow oral medicine;

    8. Volunteer to participate into this clinical trial and the informed consents must be written by patients themselves or their direct relatives. Authorized medical attorney or direct relatives can write the informed consents if it is not good for patients' treatment when consider the severity of their disease.

    Exclusion Criteria:

    1. Received anti-myeloma treatment before (not include radiotherapy, bisphosphonates or single short term steroids treatment [the dose and duration of prednisone should be no more than 40mg/d and 4 days and should discontinue this treatment within 14 days before the enrollment]);

    2. Primary or secondary plasma cell leukemia;

    3. Positive HIV tests or active infection phase of HAV, HBV and HCV; or HBV DNA copies

    104/ml；AST and ALT > 2.5*ULN (same age group);

    1. Severe diseases that threaten patients with unacceptable risks; these diseases include but are not confined to unstable heart diseases, which can be defined as cardiac accidents such as MI within 6 months, NYHA stage Ⅲ-Ⅳ heart failure, uncontrolled atrial fibrillation or hypertension and myeloma requiring long term administration of steroids or immune-inhibitors;

    2. Renal failure requiring hemodialysis or peritoneal dialysis;

    3. Severe embolic or thrombotic events before therapy;

    4. Major surgery within 30 days before being enrolled;

    5. Total obstruction of biliary tract;

    6. Glaucoma;

    7. History of malignancies except multiple myeloma unless being cured for more than 3 years;

    8. Severe allergic to osalmide capsule;

    9. Gestation, lactation or disagreed pregnancy;

    10. Severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis);

    11. Seizures requiring medicines, patients with dementias and other mental disorders who cannot understand or obey the protocol;

    12. Substance abuse, medical, psychological, or social conditions that may interfere with the subject's compliance in the study or assessment of the results of the study;

    13. Severe liver and kidney dysfunction;

    14. Patients who are considered unsuitable for enrollment by investigators.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Shanghai 10th People's Hospital Shanghai Shanghai China 200072

    Sponsors and Collaborators

    • Shanghai 10th People's Hospital
    • Shanghai Institute of Materia Medica, Chinese Academy of Sciences

    Investigators

    • Study Director: Jumei Shi, MD PhD, Shanghai 10th People's Hospital
    • Principal Investigator: Weiliang Zhu, PhD, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Jumei Shi, Professor, Shanghai 10th People's Hospital
    ClinicalTrials.gov Identifier:
    NCT03670173
    Other Study ID Numbers:
    • STPH-MM001
    First Posted:
    Sep 13, 2018
    Last Update Posted:
    May 19, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jumei Shi, Professor, Shanghai 10th People's Hospital
    Multiple myeloma, Osalmid
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell

    Study Results

    No Results Posted as of May 19, 2021