A Perspective 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 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: June 10, 2024
• Est. completion date: June 10, 2027

Study information

• Verified date: June 2024
• Source: The First Hospital of Jilin University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study was to observe the rate of MRD conversion and the impact on survival in newly diagnosed multiple myeloma (NDMM) patients with persistent MRD positivity after induction and consolidation therapy (autologous hematopoietic stem cell transplantation or consolidation of the original regimen) who were switched to high-intensity therapy, and to compare the rate of persistent MRD-negativity, progression-free survival (PFS), and overall survival (OS) between the two groups in comparison with NDMM patients who achieved MRD-negativity after the same induction and consolidation therapy.

Description:

There is still an unmet clinical need as to whether NDMM patients with persistent MRD positive would benefit from switching to high-intensity therapy. The induction regimen (Dara+/- (Vd, Rd, Pd, VRd, VPd)) was selected based on the frail or high-risk status of NDMM patients. Transplantation or consolidation and maintenance regimens were adjusted by MRD status detected by NGF.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: June 10, 2027
• Est. primary completion date: June 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject must be at least 18 years of age.

2. Subject must have documented newly diagnosed symptomatic multiple myeloma as defined by 2014 International Myeloma Working Group criteria.

3. Subject must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at one prior regimen.

4. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. Contraception must begin 4 weeks prior to dosing and continue until at least 3 months after receiving the last dose of the study drug. A woman of childbearing potential must have a negative serum or urine pregnancy tests at screening within 14 days prior to randomization.

5. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

1. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment or end-organ damage.

2. Relapsed and refractory myeloma:Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.

3. Primary refractory myeloma:Primary refractory myeloma is defined as disease that is nonresponsive in patients who have never achieved a minimal response or better with any therapy.

4. Subject is known or suspected of not being able to comply with the study protocol? Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.

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)

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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

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* 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	To explore the rate of conversion to MRD-negative after adjusting treatment in NDMM patients with persistent MRD-positive status.	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