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

NCT04063189 | Unknown Phase 2 DMC

• 1 other identifier: BiRd 2017-288-1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma in Relapse

Keywords

Clarithromycin Lenalidomide Dexamethasone Regimen; Treatment Response; Survival

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v4.03

  Through study completion,an average of 2 year

• Progression-Free Survival (PFS)

  Through study completion, an average of 2 year

• Overall Survival (OS)

  Through study completion, an average of 2 year

• Duration of Response (DOR)

  Through study completion, an average of 2 year

Other Outcomes (1)

• Health-Related Quality of Life (HRQoL)

  Every 6 months until disease progression or study completion，an average of 2 year

Study Arms (1)

First Relapsed Multiple Myeloma

EXPERIMENTAL

Drug: Clarithromycin Lenalidomide Dexamethasone (BiRd) Regimen

Interventions

Clarithromycin Lenalidomide Dexamethasone (BiRd) Regimen DRUG

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

First Relapsed Multiple Myeloma

Eligibility Criteria

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

You may qualify if:

• diagnosed as symptomatic multiple myeloma.
• 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).
• there must be measurable lesions to determine disease progression (PD): according to the IMWG 2016 efficacy evaluation criteria.
• the expected survival time is longer than 3 months.
• ECOG score less than 2 points.
• 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.
• 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%).
• 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.
• all patients were required to sign informed consent.

You may not qualify if:

• under the age of 18
• ECOG score \>2
• non secretory myeloma, defined as serum protein M \< 1g/dL, urinary M protein \< 200mg/24h and sFLCR ≤100mg/L
• there is growing demand, pregnant or lactating women within one year
• HIV infection
• activity of HBV or HCV infection
• weeks before entering the group of thromboembolic events
• not signed informed consent

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

Related Publications (12)

• Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60. doi: 10.1056/NEJMra1011442. No abstract available.

  PMID: 21410373 BACKGROUND

• 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.

  PMID: 27986429 BACKGROUND

• 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.

  PMID: 27531679 BACKGROUND

• 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.

  PMID: 27843120 BACKGROUND

• 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. doi: 10.1056/NEJMoa070596.

  PMID: 18032763 BACKGROUND

• Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa 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. doi: 10.1056/NEJMoa070594.

  PMID: 18032762 BACKGROUND

• 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.

  PMID: 23782711 BACKGROUND

• 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.

  PMID: 19626046 BACKGROUND

• 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.

  PMID: 23299315 BACKGROUND

• 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. doi: 10.1182/blood-2007-05-090258. Epub 2007 Nov 7.

  PMID: 17989313 BACKGROUND

• 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. No abstract available.

  PMID: 23625297 BACKGROUND

• 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.

  PMID: 24723438 BACKGROUND

MeSH Terms

Interventions

Clinical Protocols

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Fengyan Jin, professor

  The First Hospital of Jilin University

  STUDY DIRECTOR

Central Study Contacts

Fengyan Jin, professor

CONTACT

13844989638; fengyanjin@jlu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD, Physician in Charge of Hematology Department

Study Record Dates

• First Submitted: January 17, 2018
• First Posted: August 21, 2019
• Study Start: March 21, 2017
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: August 21, 2019

Record last verified: 2019-08

Locations

CN (1)