Clinical Trial of Clarithromycin, Lenalidomide and Dexamethasone in the Treatment of the First Relapsed Multiple Myeloma

Multiple Myeloma in Relapse Clinical Trial

Official title:

A Prospective, Multicenter, Single Arm, Phase II Clinical Trial of Clarithromycin, Lenalidomide and Dexamethasone (BiRd Regimen) in the Treatment of the First Relapsed Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04063189
• Other study ID #: BiRd 2017-288-1
• Status: Recruiting
• Phase: Phase 2
• Start date: March 21, 2017
• Est. completion date: February 1, 2020

Study information

• Verified date: August 2019
• Source: First Hospital of Jilin University
• Contact: Fengyan Jin, professor
• Phone: 13844989638
• Email: fengyanjin[@]jlu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BiRd regimen consisting of clarithromycin and Rd is safe and effective in NDMM. It can significantly increase ORR (up to 90.3%) , relief depth (≥VGPR), and prolong PFS to 43 months. In our previous study, thirty RRMM patients treated with BiRd regimen in 6 centers in China benefited.It suggested that BiRd regimen may not only improve overall efficacy of RRMM , especially long-term benefits, but also reverse Rd resistance in patients who fail to achieve any remission after multiline therapy.The study is a Prospective, Multicenter, Single Arm, Phase II Clinical Trial, which intend to recruit first relapse MM patients over 18 years old. Once included, patients will receive the treatment of Clarithromycin Lenalidomide Dexamethasone (BiRd) Regimen. (Clarithromycin 500mg，po，bid，d1-21; Lenalidomide 25mg，po，daily，d1-21 (dose according to creatinine clearance rate); Dexamethasone 20mg，po，daily，d1-2, 8-9,15-16, 22-23) And we will evaluate efficacy and adverse events of the BiRd regimen at a point of time predetermined.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 1, 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. diagnosed as symptomatic multiple myeloma.

2. the first relapse/progression with thalidomide, bortezomib or lenalidomide based current first-line treatment or resistance to the first-line treatment (previous treatment line number =1).

3. there must be measurable lesions to determine disease progression (PD): according to the IMWG 2016 efficacy evaluation criteria.

4. the expected survival time is longer than 3 months.

5. ECOG score less than 2 points.

6. the serum AST/ALT level <3 times higher than the normal value; the serum total bilirubin level<2 times of the normal value; creatinine clearance rate was =30ml/mi.

7. neutrophil count >1000/mm3 ; platelet count >75000/mm3 (if bone marrow plasma cell <50%) or >30000/mm3 (if the plasma cells in the bone marrow is not less than 50%).

8. women of childbearing age were negative for pregnancy before admission, and agreed to carry out pregnancy screening during the study (once a month until 4 weeks after the last dose), and agreed to use contraceptive measures within 3 months after the study and the last dose.

9. all patients were required to sign informed consent.

Exclusion Criteria:

1. under the age of 18

2. ECOG score >2

3. non secretory myeloma, defined as serum protein M < 1g/dL, urinary M protein < 200mg/24h and sFLCR =100mg/L

4. there is growing demand, pregnant or lactating women within one year

5. HIV infection

6. activity of HBV or HCV infection

7. 4 weeks before entering the group of thromboembolic events

8. not signed informed consent

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Neoplasms, Plasma Cell

Intervention

Drug:
• Clarithromycin Lenalidomide Dexamethasone (BiRd) Regimen
Clarithromycin 500mg,po,bid,d1-21; Lenalidomide 25mg,po,daily,d1-21 (dose according to creatinine clearance rate); Dexamethasone 20mg,po,daily,d1-2, 8-9,15-16, 22-23

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Changchun	Jilin

Sponsors (1)

Lead Sponsor	Collaborator
First Hospital of Jilin University

Country where clinical trial is conducted

China, 

References & Publications (12)

Agarwal A, Chow E, Bhutani M, Voorhees PM, Friend R, Usmani SZ. Practical Considerations in Managing Relapsed Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2017 Feb;17(2):69-77. doi: 10.1016/j.clml.2016.11.010. Epub 2016 Nov 23. Review. — View Citation

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. Erratum in: N Engl J Med. 2009 Jul 30;361(5):544. — View Citation

Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. doi: 10.1038/leu.2009.147. Epub 2009 Jul 23. — View Citation

Ghosh N, Tucker N, Zahurak M, Wozney J, Borrello I, Huff CA. Clarithromycin overcomes resistance to lenalidomide and dexamethasone in multiple myeloma. Am J Hematol. 2014 Aug;89(8):E116-20. doi: 10.1002/ajh.23733. Epub 2014 Apr 26. — View Citation

Hou J, Du X, Jin J, Cai Z, Chen F, Zhou DB, Yu L, Ke X, Li X, Wu D, Meng F, Ai H, Zhang J, Wortman-Vayn H, Chen N, Mei J, Wang J. A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol. 2013 Jun 19;6:41. doi: 10.1186/1756-8722-6-41. — View Citation

Kato H, Onishi Y, Okitsu Y, Katsuoka Y, Fujiwara T, Fukuhara N, Ishizawa K, Takagawa M, Harigae H. Addition of clarithromycin to lenalidomide/low-dose dexamethasone was effective in a case of relapsed myeloma after long-term use of lenalidomide. Ann Hematol. 2013 Dec;92(12):1711-2. doi: 10.1007/s00277-013-1761-x. Epub 2013 Apr 28. — View Citation

Niesvizky R, Jayabalan DS, Christos PJ, Furst JR, Naib T, Ely S, Jalbrzikowski J, Pearse RN, Zafar F, Pekle K, Larow A, Lent R, Mark T, Cho HJ, Shore T, Tepler J, Harpel J, Schuster MW, Mathew S, Leonard JP, Mazumdar M, Chen-Kiang S, Coleman M. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood. 2008 Feb 1;111(3):1101-9. Epub 2007 Nov 7. — View Citation

Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60. doi: 10.1056/NEJMra1011442. Review. — View Citation

Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, Laubach JP, Palumbo A, Lisby S, Basse L, Wang J, Sasser AK, Guckert ME, de Boer C, Khokhar NZ, Yeh H, Clemens PL, Ahmadi T, Lokhorst HM, Richardson PG. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016 Oct 6;128(14):1821-1828. doi: 10.1182/blood-2016-07-726729. Epub 2016 Aug 16. — View Citation

Popat R, Brown SR, Flanagan L, Hall A, Gregory W, Kishore B, Streetly M, Oakervee H, Yong K, Cook G, Low E, Cavenagh J; Myeloma UK Early Phase Clinical Trial Network. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016 Dec;3(12):e572-e580. doi: 10.1016/S2352-3026(16)30165-X. Epub 2016 Nov 12. — View Citation

Rossi A, Mark T, Jayabalan D, Christos P, Zafar F, Pekle K, Pearse R, Chen-Kiang S, Coleman M, Niesvizky R. BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma. Blood. 2013 Mar 14;121(11):1982-5. doi: 10.1182/blood-2012-08-448563. Epub 2013 Jan 8. — View Citation

Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-Related Quality of Life (HRQoL)	According to the data of SF-36 Quality of Life Questionnaire Survey	Every 6 months until disease progression or study completion,an average of 2 year
Primary	Objective response rate (ORR)	According to the criteria of IMWG 2016	Every 2 months until disease progression or study completion,an average of 2 year
Secondary	Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v4.03	According to NCI-CTCAE version 4.03	Through study completion,an average of 2 year
Secondary	Progression-Free Survival (PFS)	PFS were calculated from the enrollment to the first instance of disease progression, relapse, or death	Through study completion, an average of 2 year
Secondary	Overall Survival (OS)	OS were calculated from the time of enrollment to death or the last follow-up	Through study completion, an average of 2 year
Secondary	Duration of Response (DOR)	the time from the first assessment of CR (complete response) or PR (partial response) to the first PD (Progressive Disease) or any cause of death	Through study completion, an average of 2 year