Safety and Efficacy Assessments of Osalmid in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Safety and Efficacy Assessments of Osalmid in the Treatment of Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03670173
• Other study ID #: STPH-MM001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 1, 2018
• Est. completion date: May 18, 2021

Study information

• Verified date: May 2021
• Source: Shanghai 10th People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: May 18, 2021
• Est. primary completion date: May 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 = 1.5*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;

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);

4. 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 ?-? heart failure, uncontrolled atrial fibrillation or hypertension and myeloma requiring long term administration of steroids or immune-inhibitors;

5. Renal failure requiring hemodialysis or peritoneal dialysis;

6. Severe embolic or thrombotic events before therapy;

7. Major surgery within 30 days before being enrolled;

8. Total obstruction of biliary tract;

9. Glaucoma;

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

11. Severe allergic to osalmide capsule;

12. Gestation, lactation or disagreed pregnancy;

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

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

15. 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;

16. Severe liver and kidney dysfunction;

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
China	Shanghai 10th People's Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai 10th People's Hospital	Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

References & Publications (11)

Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, de Vivo A, Testoni N, Nicci C, Terragna C, Grafone T, Perrone G, Ceccolini M, Tura S, Baccarani M; Bologna 2002 study. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005 Jul 1;106(1):35-9. Epub 2005 Mar 10. — View Citation

Kapoor P, Fonseca R, Rajkumar SV, Sinha S, Gertz MA, Stewart AK, Bergsagel PL, Lacy MQ, Dingli DD, Ketterling RP, Buadi F, Kyle RA, Witzig TE, Greipp PR, Dispenzieri A, Kumar S. Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapie. Mayo Clin Proc. 2010 Jun;85(6):532-7. doi: 10.4065/mcp.2009.0677. — View Citation

Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. doi: 10.1038/leu.2008.291. Epub 2008 Oct 30. Review. Erratum in: Leukemia. 2014 Apr;28(4):980. — View Citation

Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, Dispenzieri A, Fonseca R, Sher T, Kyle RA, Lin Y, Russell SJ, Kumar S, Bergsagel PL, Zeldenrust SR, Leung N, Drake MT, Kapoor P, Ansell SM, Witzig TE, Lust JA, Dalton RJ, Gertz MA, Stewart AK, Rajkumar SV, Chanan-Khan A, Lacy MQ; Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013 Apr;88(4):360-76. doi: 10.1016/j.mayocp.2013.01.019. Erratum in: Mayo Clin Proc. 2013 Jul;88(7):777. Stewart, Keith [corrected to Stewart, A Keith]. — View Citation

Murakami H, Handa H, Abe M, Iida S, Ishii A, Ishikawa T, Ishida T, Oota M, Ozaki S, Kosaka M, Sakai A, Sawamura M, Shimazaki C, Shimizu K, Takagi T, Hata H, Fukuhara T, Fujii H, Miyata A, Wakayama T, Takatsuki K. Low-dose thalidomide plus low-dose dexamethasone therapy in patients with refractory multiple myeloma. Eur J Haematol. 2007 Sep;79(3):234-9. Epub 2007 Jul 26. — View Citation

Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19. — View Citation

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26. Review. — View Citation

Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J; International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011 May 5;117(18):4691-5. doi: 10.1182/blood-2010-10-299487. Epub 2011 Feb 3. — View Citation

Rajkumar SV, Rosiñol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Bladé 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. — View Citation

Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418-23. doi: 10.14694/EDBK_159009. Review. — View Citation

Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L, Sengsayadeth S, Abidi M, Hari P, Mohty M, Chen YB, Koreth J, Landau H, Lazarus H, Leather H, Majhail N, Nath R, Osman K, Perales MA, Schriber J, Shaughnessy P, Vesole D, Vij R, Wingard J, Giralt S, Savani BN; American Society for Blood and Marrow Transplantation. Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015 Jul;21(7):1155-66. doi: 10.1016/j.bbmt.2015.03.002. Epub 2015 Mar 11. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate	M protein qualification in serum and/or urine decline of at least 25%, 50%, 75%, or 90%	at week16
Secondary	time to progression	from the start of therapy to disease progression	at week 48
Secondary	duration of response	from the time response was achieved to disease progression or death	at week 48
Secondary	progression-free survival	from study entry to disease progression or death	at week 48
Secondary	overall survival	from the date of study entry to the date of death or last follow-up	at week 48