A Perspective, Single Center Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment

Multiple Myeloma Clinical Trial

— MRD  

Official title:

A Perspective, Single Center Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06109233
• Other study ID #: MRD 2023
• Status: Not yet recruiting
• Start date: December 30, 2023
• Est. completion date: December 30, 2026

Study information

• Verified date: November 2023
• Source: The First Hospital of Jilin University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators designed the present study with the aim of observing the rate of MRD conversion and its impact on survival in primary multiple myeloma (NDMM) patients with persistent MRD positivity after induction and consolidation therapy (autologous hematopoietic stem cell transplantation or consolidation of the original regimen) after tonification therapy and comparing them with the same NDMM patients who obtained MRD negativity after induction and consolidation therapy, and observing the rate of persistent MRD negativity, progression-free survival (PFS), and overall survival in the two groups. progression survival (PFS) and overall survival (OS).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age of 18 years or older and gender;

2. Diagnosed with primary multiple myeloma according to the 2014 IMWG multiple myeloma diagnostic criteria, receiving induction and consolidation therapy to achieve partial remission (PR) and above, and MRD-negative, or persistently MRD-positive and agreeing to adjust the treatment regimen;

3. No progression of extramedullary plasmacytoma or new bone destruction and extramedullary plasmacytoma confirmed by whole-body low-dose CT, MRI, or PET-CT after induction and consolidation therapy;

4. Females of childbearing age must have a negative pregnancy test prior to enrollment and agree to use contraception during the study and for 3 months after the last treatment;

5. Subjects and family members agree to participate in the study and sign an informed consent form.

Exclusion Criteria:

1. Failure to achieve PR after induction and consolidation therapy;

2. Relapsed multiple myeloma;

3. disagreed to participate in this clinical study.

Related Conditions & MeSH terms

• Minimal Residual Disease
• Multiple Myeloma
• Neoplasm, Residual
• Neoplasms, Plasma Cell

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
FengYan Jin

References & Publications (26)

Alonso S, Hernandez D, Chang YT, Gocke CB, McCray M, Varadhan R, Matsui WH, Jones RJ, Ghiaur G. Hedgehog and retinoid signaling alters multiple myeloma microenvironment and generates bortezomib resistance. J Clin Invest. 2016 Dec 1;126(12):4460-4468. doi: 10.1172/JCI88152. Epub 2016 Oct 24. — View Citation

Anderson KC. Progress and Paradigms in Multiple Myeloma. Clin Cancer Res. 2016 Nov 15;22(22):5419-5427. doi: 10.1158/1078-0432.CCR-16-0625. — View Citation

Anderson KC. Should minimal residual disease negativity be the end point of myeloma therapy? Blood Adv. 2017 Mar 14;1(8):517-521. doi: 10.1182/bloodadvances.2016000117. eCollection 2017 Mar 14. — View Citation

Avet-Loiseau H. Minimal Residual Disease by Next-Generation Sequencing: Pros and Cons. Am Soc Clin Oncol Educ Book. 2016;35:e425-30. doi: 10.1200/EDBK_159088. — View Citation

Davies FE, Forsyth PD, Rawstron AC, Owen RG, Pratt G, Evans PA, Richards SJ, Drayson M, Smith GM, Selby PJ, Child JA, Morgan GJ. The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol. 2001 Mar;112(3):814-9. doi: 10.1046/j.1365-2141.2001.02530.x. — View Citation

Flores-Montero J, Sanoja-Flores L, Paiva B, Puig N, Garcia-Sanchez O, Bottcher S, van der Velden VHJ, Perez-Moran JJ, Vidriales MB, Garcia-Sanz R, Jimenez C, Gonzalez M, Martinez-Lopez J, Corral-Mateos A, Grigore GE, Fluxa R, Pontes R, Caetano J, Sedek L, Del Canizo MC, Blade J, Lahuerta JJ, Aguilar C, Barez A, Garcia-Mateo A, Labrador J, Leoz P, Aguilera-Sanz C, San-Miguel J, Mateos MV, Durie B, van Dongen JJM, Orfao A. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017 Oct;31(10):2094-2103. doi: 10.1038/leu.2017.29. Epub 2017 Jan 20. — View Citation

Harousseau JL, Avet-Loiseau H. Minimal Residual Disease Negativity Is a New End Point of Myeloma Therapy. J Clin Oncol. 2017 Sep 1;35(25):2863-2865. doi: 10.1200/JCO.2017.73.1331. Epub 2017 May 19. No abstract available. — View Citation

Jelinek T, Bezdekova R, Zatopkova M, Burgos L, Simicek M, Sevcikova T, Paiva B, Hajek R. Current applications of multiparameter flow cytometry in plasma cell disorders. Blood Cancer J. 2017 Oct 20;7(10):e617. doi: 10.1038/bcj.2017.90. Erratum In: Blood Cancer J. 2018 Jan 19;8(1):e621. — View Citation

Kumar SK, Rajkumar SV. The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018 Jul;15(7):409-421. doi: 10.1038/s41571-018-0018-y. — View Citation

Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers. 2017 Jul 20;3:17046. doi: 10.1038/nrdp.2017.46. — View Citation

Lahuerta JJ, Paiva B, Vidriales MB, Cordon L, Cedena MT, Puig N, Martinez-Lopez J, Rosinol L, Gutierrez NC, Martin-Ramos ML, Oriol A, Teruel AI, Echeveste MA, de Paz R, de Arriba F, Hernandez MT, Palomera L, Martinez R, Martin A, Alegre A, De la Rubia J, Orfao A, Mateos MV, Blade J, San-Miguel JF; GEM (Grupo Espanol de Mieloma)/PETHEMA (Programa para el Estudio de la Terapeutica en Hemopatias Malignas) Cooperative Study Group. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials. J Clin Oncol. 2017 Sep 1;35(25):2900-2910. doi: 10.1200/JCO.2016.69.2517. Epub 2017 May 12. — View Citation

Landgren O, Devlin S, Boulad M, Mailankody S. Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis. Bone Marrow Transplant. 2016 Dec;51(12):1565-1568. doi: 10.1038/bmt.2016.222. Epub 2016 Sep 5. — View Citation

Maiso P, Huynh D, Moschetta M, Sacco A, Aljawai Y, Mishima Y, Asara JM, Roccaro AM, Kimmelman AC, Ghobrial IM. Metabolic signature identifies novel targets for drug resistance in multiple myeloma. Cancer Res. 2015 May 15;75(10):2071-82. doi: 10.1158/0008-5472.CAN-14-3400. Epub 2015 Mar 13. — View Citation

Martinez-Lopez J, Lahuerta JJ, Pepin F, Gonzalez M, Barrio S, Ayala R, Puig N, Montalban MA, Paiva B, Weng L, Jimenez C, Sopena M, Moorhead M, Cedena T, Rapado I, Mateos MV, Rosinol L, Oriol A, Blanchard MJ, Martinez R, Blade J, San Miguel J, Faham M, Garcia-Sanz R. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014 May 15;123(20):3073-9. doi: 10.1182/blood-2014-01-550020. Epub 2014 Mar 19. — View Citation

Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, Sherrington P, Samur MK, Georgieva A, Anderson KC, Gregory WM. Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis. JAMA Oncol. 2017 Jan 1;3(1):28-35. doi: 10.1001/jamaoncol.2016.3160. — View Citation

Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, Flores-Montero J, Gutierrez NC, Martin-Ramos ML, Martinez-Lopez J, Ocio EM, Hernandez MT, Teruel AI, Rosinol L, Echeveste MA, Martinez R, Gironella M, Oriol A, Cabrera C, Martin J, Bargay J, Encinas C, Gonzalez Y, Van Dongen JJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San Miguel JF; Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas (GEM/PETHEMA) Cooperative Study Groups. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319. Epub 2016 Apr 26. — View Citation

Paiva B, Puig N, Cedena MT, de Jong BG, Ruiz Y, Rapado I, Martinez-Lopez J, Cordon L, Alignani D, Delgado JA, van Zelm MC, Van Dongen JJ, Pascual M, Agirre X, Prosper F, Martin-Subero JI, Vidriales MB, Gutierrez NC, Hernandez MT, Oriol A, Echeveste MA, Gonzalez Y, Johnson SK, Epstein J, Barlogie B, Morgan GJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San-Miguel JF. Differentiation stage of myeloma plasma cells: biological and clinical significance. Leukemia. 2017 Feb;31(2):382-392. doi: 10.1038/leu.2016.211. Epub 2016 Aug 1. — View Citation

Paiva B, van Dongen JJ, Orfao A. New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood. 2015 May 14;125(20):3059-68. doi: 10.1182/blood-2014-11-568907. Epub 2015 Apr 2. — View Citation

Paiva B, Vidriales MB, Cervero J, Mateo G, Perez JJ, Montalban MA, Sureda A, Montejano L, Gutierrez NC, Garcia de Coca A, de Las Heras N, Mateos MV, Lopez-Berges MC, Garcia-Boyero R, Galende J, Hernandez J, Palomera L, Carrera D, Martinez R, de la Rubia J, Martin A, Blade J, Lahuerta JJ, Orfao A, San Miguel JF; GEM (Grupo Espanol de MM)/PETHEMA (Programa para el Estudio de la Terapeutica en Hemopatias Malignas) Cooperative Study Groups. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008 Nov 15;112(10):4017-23. doi: 10.1182/blood-2008-05-159624. Epub 2008 Jul 31. — View Citation

Perrot A, Lauwers-Cances V, Corre J, Robillard N, Hulin C, Chretien ML, Dejoie T, Maheo S, Stoppa AM, Pegourie B, Karlin L, Garderet L, Arnulf B, Doyen C, Meuleman N, Royer B, Eveillard JR, Benboubker L, Dib M, Decaux O, Jaccard A, Belhadj K, Brechignac S, Kolb B, Fohrer C, Mohty M, Macro M, Richardson PG, Carlton V, Moorhead M, Willis T, Faham M, Anderson KC, Harousseau JL, Leleu X, Facon T, Moreau P, Attal M, Avet-Loiseau H, Munshi N. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood. 2018 Dec 6;132(23):2456-2464. doi: 10.1182/blood-2018-06-858613. Epub 2018 Sep 24. — View Citation

Puig N, Sarasquete ME, Balanzategui A, Martinez J, Paiva B, Garcia H, Fumero S, Jimenez C, Alcoceba M, Chillon MC, Sebastian E, Marin L, Montalban MA, Mateos MV, Oriol A, Palomera L, de la Rubia J, Vidriales MB, Blade J, Lahuerta JJ, Gonzalez M, Miguel JF, Garcia-Sanz R. Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry. Leukemia. 2014 Feb;28(2):391-7. doi: 10.1038/leu.2013.217. Epub 2013 Jul 17. — View Citation

Rawstron AC, Child JA, de Tute RM, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Feyler S, Ross FM, Cook G, Jackson GH, Morgan GJ, Owen RG. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol. 2013 Jul 10;31(20):2540-7. doi: 10.1200/JCO.2012.46.2119. Epub 2013 Jun 3. Erratum In: J Clin Oncol. 2013 Dec 1;31(34):4383. — View Citation

Rawstron AC, Gregory WM, de Tute RM, Davies FE, Bell SE, Drayson MT, Cook G, Jackson GH, Morgan GJ, Child JA, Owen RG. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction. Blood. 2015 Mar 19;125(12):1932-5. doi: 10.1182/blood-2014-07-590166. Epub 2015 Feb 2. — View Citation

Silvennoinen R, Lundan T, Kairisto V, Pelliniemi TT, Putkonen M, Anttila P, Huotari V, Mantymaa P, Siitonen S, Uotila L, Penttila TL, Juvonen V, Selander T, Remes K. Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma. Blood Cancer J. 2014 Oct 10;4(10):e250. doi: 10.1038/bcj.2014.69. — View Citation

Sonneveld P. Should minimal residual disease negativity not be the end point of myeloma therapy? Blood Adv. 2017 Mar 14;1(8):522-525. doi: 10.1182/bloodadvances.2017000109. eCollection 2017 Mar 14. — View Citation

Yang P, Xu W, Liang X, Yu S, Yi X, Liu M, Tian M, Yue T, Zhang Y, Yan Y, Hu Z, Guo Q, Zhang N, Wang J, Sun X, Hu R, Kumar SK, Dai Y, Jin F. Dynamic monitoring of minimal residual disease in newly-diagnosed multiple myeloma. Am J Hematol. 2023 Mar;98(3):E61-E64. doi: 10.1002/ajh.26810. Epub 2022 Dec 21. No abstract available. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	explore the molecular basis for the dynamic changes and differences in MRD	Bone puncture samples from routine clinical consultations were collected, and single-cell transcriptome sequencing technology was applied to analyze and compare the differences in MM cells (clones) and bone marrow microenvironment (including immunity, inflammation, and stroma) of MRD-transformed and non-transformed patients after adjusting the treatment regimen, using the samples before adjusting the treatment regimen as the baseline control, in order to explore the molecular basis for the dynamic changes and differences in MRD	through study completion, up to 2 years
Other	explore the elderly (especially debilitated) patients' MRD-adjusted treatment	For patients =65 years old, through the adjusted treatment-adjusted MRD-negative rates to explore the impact of strategy adjustment on elderly patients	through study completion, up to 2 years
Primary	Adjusted treatment-adjusted MRD-negative rates	Adjusted treatment-adjusted MRD-negative rates in NDMM patients with persistent MRD positivity after induction and consolidation therapy. In this context, MRD-negativity was defined as bone marrow MRD-negativity confirmed by next-generation flow cytometry (NGF) or next-generation sequencing technology (NGS).	through study completion, up to 2 years
Secondary	Progression-Free Survival (PFS)	PFS were calculated from the enrollment to the first instance of disease progression, relapse, or death	through study completion, up to 2 years
Secondary	Overall Survival (OS)	OS were calculated from the time of enrollment to death or the last follow-up	through study completion, up to 2 years
Secondary	Persistent MRD-negative rates and survival	Persistent MRD-negative rates and survival (including PFS and OS) in both groups compared to NDMM patients who achieved MRD-negativity after the same induction and consolidation therapy	through study completion, up to 2 years
Secondary	Treatment related adverse event(TRAE)	Toxicity and safety will be reported based on the adverse events, as graded by CTCAE V5 and determined by routine clinical assessments.	through study completion, up to 2 years