Safety and Efficacy Assessments of Osalmid in Multiple Myeloma

NCT03670173 | Unknown Phase 1

• 1 other identifier: STPH-MM001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Myeloma

Keywords

Multiple myeloma, Osalmid

Outcome Measures

Primary Outcomes (1)

• overall response rate

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

  at week16

Secondary Outcomes (4)

• time to progression

  at week 48

• duration of response

  at week 48

• progression-free survival

  at week 48

• overall survival

  at week 48

Study Arms (1)

Osalmid

EXPERIMENTAL

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

Interventions

Osalmid DRUG

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.

Also known as: 2-hydroxy-N-(4-hydroxyphenyl)-benzamide

Osalmid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with age≥ 18 years old who are willing to receive the treatment of osalmid;
• 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);
• Eastern Cancer Organization Group (ECOG) score≤2 and expected survival\>2 months;
• Belongs to "measurable disease": serum M protein ≥10g/L and/or 24 hour urine M protein ≥200mg;
• No active infectious diseases;
• 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 ≤ 1.5\*ULN (same age group); b. AST and ALT ≤ 2.5\*ULN (same age group); c. Cardiac enzyme \< 2\*ULN (same age group); d. Normal ejection fraction confirmed in echo;
• Able to swallow oral medicine;
• 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.

You may not qualify if:

• Received anti-myeloma treatment before (not include radiotherapy, bisphosphonates or single short term steroids treatment \[the dose and duration of prednisone should be no more than 40mg/d and 4 days and should discontinue this treatment within 14 days before the enrollment\]);
• Primary or secondary plasma cell leukemia;
• 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);
• 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;
• Renal failure requiring hemodialysis or peritoneal dialysis;
• Severe embolic or thrombotic events before therapy;
• Major surgery within 30 days before being enrolled;
• Total obstruction of biliary tract;
• Glaucoma;
• History of malignancies except multiple myeloma unless being cured for more than 3 years;
• Severe allergic to osalmide capsule;
• Gestation, lactation or disagreed pregnancy;
• Severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis);
• Seizures requiring medicines, patients with dementias and other mental disorders who cannot understand or obey the protocol;
• 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;

Sponsors & Collaborators

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

Study Sites (1)

Shanghai 10th People's Hospital

Shanghai, Shanghai Municipality, 200072, China

Location

Related Publications (12)

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• Rajkumar SV, Rosinol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Blade J. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008 May 1;26(13):2171-7. doi: 10.1200/JCO.2007.14.1853. Epub 2008 Mar 24.

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• Xie Y, Wang Y, Xu Z, Lu Y, Song D, Gao L, Yu D, Li B, Chen G, Zhang H, Feng Q, Zhang Y, Hu K, Huang C, Peng Y, Wu X, Mao Z, Shao J, Zhu W, Shi J. Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma. J Biomed Sci. 2022 May 12;29(1):32. doi: 10.1186/s12929-022-00813-2.

  PMID: 35546402 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jumei Shi, MD PhD

  Shanghai 10th People's Hospital

  STUDY DIRECTOR

• Weiliang Zhu, PhD

  Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: multi-center, single-arm, open-label, non-blind

Study Record Dates

• First Submitted: September 9, 2018
• First Posted: September 13, 2018
• Study Start: October 1, 2018
• Primary Completion: May 18, 2021
• Study Completion: May 18, 2021
• Last Updated: May 19, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)