The Asian Myeloma Network (AMN) has developed their own clinical trial network to facilitate early access to drugs in Asian countries and to conduct clinical trials/studies that answer questions relevant to Asians.
How the IMF's Asian Myeloma Network Conducts Its Studies
To establish a way to conduct multi-center, multi-country clinical trials within Asia took two years. Now, the International Myeloma Foundation's Asian Myeloma Network (AMN) can partner with principal investigators coordinating trials across multiple sites and with a clinical research organization (CRO) that is in charge of data capture, statistical analysis, regular reports, and pharmacovigilance. The AMN also partners with sites in charge of recruitment, data integrity and completeness, and meeting the regulatory requirements.
AMN001 Clinical Trial Results Are Published
In December 2014, the AMN partnered with Celgene for our first trial, AMN001. This study examined the use of pomalidomide and dexamethasone in relapse myeloma; it was the first large-scale study using this drug combination for relapsed multiple myeloma patients in Asia. For patients who experienced a sub-optimal response to this combination, researchers used cyclophosphamide. The goal was to optimize the use of pomalidomide in Asia.
The trial proved the AMN’s ability to collaborate with pharmaceutical companies, to recruit patients, and to perform results-based analyses.The trial successfully accrued 130 patients across South Korea, Japan, Singapore, Hong Kong, and Taiwan within 18 months. Data from an interim analysis was presented at the American Society of Hematology (ASH) Meeting in December 2016 and at the European Hematology Association (EHA) in 2017. The trial was completed in 2018, the results were published in Blood Cancer Journal 2019.
AMN002 Clinical Trial Results Are Published
Due to the success of our first trial, many other groups have expressed interest in working with the AMN. Our second trial, AMN002, investigated the use of a proteasome inhibitor (PI), carfilzomib, in combination with an immunomodulatory drug (IMiD) thalidomide and dexamethasone in relapsed myeloma. This combination was considered more affordable and applicable for multiple myeloma patients in Asia-Pacific region.
This trial was supported by Amgen in collaboration with the Australian Leukemia and Lymphoma Group (ALLG), and was conducted in parallel at AMN sites in Singapore, Taiwan and South Korea as well as ALLG sites in Australia and New Zealand. The first AMN patient was enrolled in September 2017. A total of 93 patients of Asian or non-Asian ethnicity (Australia n=49; Asia n=41) were enrolled for this trial. The interim analysis was presented at IMGW 2019 and ASH 2020. The trial concluded successfully in 2022. The results were published in Haematologica in 2023.
AMN003 Clinical Trial Accepted As an Oral Presentation in the 2023 American Society of Hematology Annual Meeting and Exposition
A third trial, AMN003, supported by Celgene, is a phase II, multiple-site, multiple-country, randomized, open-labelled, two-arm treatment trial of relapsed and/or refractory multiple myeloma (RRMM), It compares pomalidomide in combination with cyclophosphamide and dexamethasone (PCD) to solely pomalidomide and dexamethasone (PD). It was hypothesized that PCD would be better than PD and should be the standard pomalidomide-containing regimen for relapsed myeloma patients.
This trial commenced in Singapore and Japan in September 2017, with 120 subjects enrolled at 25 sites across various countries and regions in Asia, including Singapore, Japan, Hong Kong, Taiwan, and Malaysia. The interim analysis results were presented at ASH 2020. The study was completed in 2022, demonstrating that the combination treatment of PCd significantly prolonged progression-free survival, improved overall response rate (ORR), and prolonged depth of response (DOR) over Pd treatment in Asian subjects with RRMM. The abstract of AMN003 study was accepted as an oral presentation at ASH 2022, and a manuscript is under preparation for publication.
Two Additional Clinical Trials: AMN004 and AMN006
In addition, two other trials in partnership with Johnson & Johnson, AMN004 and AMN006 were launched in 2018 and 2019 respectively. AMN004 explored the use of daratumumab in combination with thalidomide and dexamethasone in relapse myeloma. AMN006 focused on using daratumumab in combination with Velcade (bortezomib) and dexamethasone in newly diagnosed non-transplant eligible myeloma. Daratumumab, a humanized antibody against CD38 and a promising new drug which is well tolerated, has shown that addition of dexamethasone or thalidomide has significantly improved response and enhanced the treatment efficacy of daratumumab. This set the stage for combinations with daratumumab to increase efficacy and improve outcomes of patients in both the relapse refractory and newly diagnosed settings.
The AMN004, a phase II, multiple-site, multiple-country, single-arm trial of RRMM, was conducted in Singapore and South Korea, enrolling its first patient in May 2018. Interim analysis results were presented at ASH 2020. A total of 70 subjects were enrolled for AMN004 trial, the trial was completed in May 2023. The results have demonstrated that the combination of daratumumab, thalidomide, and dexamethasone is effective in RRMM patients, providing a cost-effective option for daratumumab-based triplet combinations. The results were represented at ASH 2023, and a manuscript has been submitted to a peer-reviewed for publication.
Different from the previous AMN trials focused on relapsed myeloma, AMN006 is a phase II, multiple-site, single-arm trial of the newly diagnosed multiple myeloma. Survival of non-transplant eligible (NTE) multiple myeloma patients tends to be inferior to that of the transplantable population. Yet, there has been improvement in survival compared to the non-novel agent era. Improving the survival of non-transplant-eligible (NTE) myeloma is an unmet need. The trial enrolled 27 patients, and the primary results were presented at ASH 2023.
The final statistical analysis will be completed by October 2024, with the expectation that the study will provide valuable information on the depth of response, survival, safety, and efficacy of this combination for the newly diagnosed transplant-ineligible multiple myeloma population.
As a side note, the AMN005 clinical trial was canceled by the industry sponsor Celgene in 2018.
AMN007 Clinical Trial Put on Hold
The AMN007 study, developed in collaboration with AbbVie, was intended to combine venetoclax with Velcade and dexamethasone for relapsed patients with extramedullary plasmacytomas. However, the trial was permanently put on hold in 2019 due to concern of safety before it commenced.
AMN008 Clinical Trial Scheduled to Launch
The AMN008, supported by Sanofi, is a prospective, multicenter, single-arm, open-label phase II trial to assess the efficacy of especially deep responses in the form of stringent complete response (sCR) and minimal residual disease (MRD) negativity achieved by using the combination of isatuximab, lenalidomide, and dexamethasone in frontline treatment of transplant-ineligible (TIE) myeloma patients. The AMN008 trial is scheduled to launch at the sites in Singapore, South Korea, and Australia, with the first patient expected to be enrolled in early 2025.
AMN009 Clinical Trial Accrual Is Ongoing
In multiple myeloma, patients with non-measurable disease, impaired renal function, extramedullary relapse, or central-nervous-system-involved myeloma are frequently excluded from clinical trials, and no available drugs have been adequately studied in these populations.
The AMN009 trial was developed in collaboration with ALLG and supported by Antengene, aims to establish a platform and to evaluate this combination of selinexor, pomalidomide, and dexamethasone across all the four organ MM groups (strata) of patients who have previously had no prospect of enrolment in clinical trials. AMN009 is a phase II, multiple-center, multiple-country trial across Australia and different Asia countries and regions including South Korea, Singapore, China, Hong Kong, and Taiwan. The first ALLG patient was enrolled in July 2024, and the first AMN patient was enrolled in September 2024. The recruitment is ongoing at AMN and ALLG sites, and aims to recruit 140 patients by 2025.
AMN010 Clinical Trial's Interim Analysis Results Are Submitted to the 2024 American Society of Hematology Annual Meeting and Exposition
The AMN010, supported by GSK, differs from the above AMN trials, as it is a multi-country, multi-site retrospective observational medical chart review study of second-line, third-line, or fourth-line multiple myeloma patients from participating AMN sites in Singapore, China, Hong Kong, Taiwan, South Korea, and Japan.
Given the heterogeneity of the disease and the numerous permutation and combination of drugs being used for the treatment of relapsed disease, it has become increasingly difficult to define the natural history of relapsed myeloma. This study is expected to establish a benchmark for anticipated outcomes in patients who have relapsed and/or refractory multiple myeloma. The study data capture started in October 2023, and the recruitment target of 1005 subjects was completed in August 2024. The interim analysis results have been submitted to the American Society of Hematology (ASH) 2024, with the final statistical analysis expected in the early of 2025.
AMN011 Clinical Trial Begins Accrual in South Korea
The AMN011, supported by Sanofi, is a multinational, multi-center, prospective, randomized, open-label, phase II study to evaluate whether the combination of isatuximab, bortezomib, lenalidomide, and dexamethasone for induction therapy (I-VRd). Followed by post-autologous stem cell transplantation (ASCT) consolidation I-VRd, improves the depth of response in newly diagnosed multiple myeloma eligible patients for transplantation. A total of 188 subjects will be enrolled in South Korea and Singapore for this trial. The enrollment commenced in South Korea in the middle of 2024, four patients had been enrolled as of August 2024.
The AMN studies have been pivotal in exploring various novel treatment regiments and have covered different types of multiple myeloma (MM) patients including relapsed/refractory, newly diagnosed, transplant-eligible or -ineligible, and orphan MM patients. These collaborations will strengthen partnerships between the AMN, biopharma companies, and institutions; establish effective and low-cost combinations of novel therapies that are relevant to Asia; and raise the profiles of the Asian community in the field of multiple myeloma research and treatments.
The Asian Myeloma Network hopes to one day leave a lasting mark not just on multiple myeloma in Asia, but also throughout the world.
AMN Clinical Trials
- AMN001: Efficacy and Toxicity Study of Pomalidomide and Dexamethasone in Patients Who Have Relapsed After Exposure to Lenalidomide and Bortezomib
https://clinicaltrials.gov/ct2/show/NCT02158702 - AMN002: Carfilzomib Thalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
https://clinicaltrials.gov/ct2/show/NCT03140943 - AMN003: Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma
https://clinicaltrials.gov/ct2/show/NCT03143049 - AMN004: Phase 2 study of daratumumab in combination with thalidomide and dexamethasone in relapse and / or refractory myeloma https://clinicaltrials.gov/ct2/show/NCT03143036
- AMN006: Phase 2 study of daratumumab in combination with bortezomib and dexamethasone in newly diagnosed multiple myeloma https://clinicaltrials.gov/ct2/show/NCT03695744
- AMN008: Minimal Residual Disease response adapted approach using Isatuximab Lenalidomide and Steroid dexamethasone in frontline treatment of transplant ineligible myeloma patients: Milestone study. Pending for registration @clinicaltrials.gov.
- AMN009: Novel Combinations for Orphan Myeloma: The NORM Platform study: Treatment Specific Appendix - Selinexor, Pomalidomide, Dexamethasone (SPd) ANZCTR - Registration (ACTRN12622001313729)
- AMN010: Asian Myeloma Network Network Study of the Natural History of Relapsed/Refractory Multiple Myleoma After Progression of One or Two Lines of Prior Lines of Therapy. Clinicaltrials.gov registration: not applicable
- AMN011: Randomized Phase II study of induction isatuximab, bortezomib, lenalidomide, and dexamethasone (I-VRD) followed by autologous stem cell transplantation with or without consolidation I-VRD in patients with transplant-eligible newly diagnosed multiple myeloma (ICON Study) CRIS란? (nih.go.kr) (KCT0009297)
Treatment Access
- IMF’s Asian Myeloma Network Succeeds in Providing Access to Pomalidomide in Asia
- Bringing Next Generation Flow Cytometry to Japan
Publications
Abstracts
Articles
- Kim, K., Lee, J.H., Kim, J.S., Min, C.K., Yoon, S.S., Shimizu, K., Chou, T., Kosugi, H., Suzuki, K., Chen, W., Hou, J., Lu, J., Huang, X.-J., Huang, S.-Y., Chng, W.J., Tan, D., Teoh, G., Chim, C.S., Nawarawong, W., Siritanaratkul, N. and Durie, B.G. (2014), Clinical profiles of multiple myeloma in Asia—An Asian Myeloma Network study. Am. J. Hematol., 89: 751-756. https://doi.org/10.1002/ajh.23731
- Ninkovic S, Harrison SJ, Lee J-J, Murphy N, Lee JH, Estell J, Chen VM, Horvath N, Kim K, Eek R, Augustson B, Bang S-M, Huang S-Y, Rajagopal R, Szabo F, Engeler D, Butcher BE, Mollee P, Durie B, Chng WJ, Quach H. Carfilzomib, thalidomide, and dexamethasone are safe and effective in relapsed and/or refractory multiple myeloma: final report of the single-arm, multicenter, phase II ALLG MM018/AMN002 study. Haematologica 2024;109(7):2229-2238; https://doi.org/10.3324/haematol.2023.284238.
- Soekojo, C.Y., Kim, K., Huang, SY. et al. Pomalidomide and dexamethasone combination with additional cyclophosphamide in relapsed/refractory multiple myeloma (AMN001)—a trial by the Asian Myeloma Network. Blood Cancer J. 9, 83 (2019). https://doi.org/10.1038/s41408-019-0245-1
- Daryl Tan, Kihyun Kim, Jin Seok Kim, Hyeon-Seok Eom, Gerrard Teoh, Kiat Hoe Ong, Yeow Tee Goh, Brian G.M. Durie, Wee Joo Chng, and Jae Hoon Lee. The impact of upfront versus sequential use of bortezomib among patients with newly diagnosed multiple myeloma (MM): A joint analysis of the Singapore MM Study Group and the Korean MM Working Party for the Asian myeloma network. Leukemia Research, 37: 1070-1076. https://doi.org/10.1016/j.leukres.2013.06.008.
- Tan, Daryl et al. Management of multiple myeloma in Asia: resource-stratified guidelines. The Lancet Oncology, Volume 14, Issue 12, e571 - e581.
