Epunamin Combined With DECP for Relapsed/Refractory Multiple Myeloma

Официальное название

A Multicenter Real-World Study Evaluating Epunamin in Combination With a DECP-Based Regimen for Relapsed/Refractory Multiple Myeloma

Обзор

Background: Multiple Myeloma remains an incurable hematologic malignancy, and outcomes for relapsed/refractory multiple myeloma (RRMM) remain unsatisfactory despite advances in therapy. This study aims to evaluate the efficacy and safety of Epunamin combined with a DECP-based regimen in a real-world clinical setting. Methods: This multicenter, single-arm, real-world observational study will enroll 48 patients aged 18-75 years with RRMM diagnosed according to revised IMWG criteria who have received at least one prior systemic treatment. Eligible patients must have an ECOG performance status of 0-3, adequate treatment compliance, and written informed consent. Key exclusion criteria include severe cardiac, pulmonary, hepatic, or renal dysfunction; unresolved prior treatment toxicity above grade 1; grade ≥2 peripheral neuropathy or grade 1 with pain; severe infection within 14 days; plasma cell leukemia; psychiatric disorders affecting compliance; pregnancy or lactation; recent other malignancies; hypersensitivity to study drugs; HIV infection; participation in another clinical trial within 30 days; or any condition deemed unsuitable by investigators. Endpoints: The primary endpoint is overall response rate (ORR) after four treatment cycles. Secondary endpoints include very good partial response (VGPR), complete response (CR), stringent complete response (sCR), minimal residual disease (MRD), duration of response (DOR), and time to next treatment (TTNT), assessed according to revised IMWG criteria. Statistical Analysis: Continuous variables will be summarized using mean, median, standard deviation, minimum, and maximum values. Normally distributed data will be analyzed using Student's t-test or ANOVA, while non-normally distributed data will use rank-sum tests. Categorical variables will be analyzed using chi-square or Fisher's exact tests, and ordinal variables by Ridit analysis or nonparametric tests. Survival outcomes including progression-free survival (PFS) and overall survival (OS) will be estimated using Kaplan-Meier analysis and compared by log-rank test. A two-sided P value \<0.05 will be considered statistically significant. Study Period: October 2025 to September 2027.

Подробное описание

Background:

Multiple Myeloma remains an incurable plasma cell malignancy, and patients with relapsed/refractory disease continue to face limited therapeutic options and poor clinical outcomes. Epunamin, in combination with a DECP-based regimen, may provide a novel therapeutic strategy in this setting. However, evidence from real-world clinical practice remains limited.

Methods:

This is a multicenter, single-arm, real-world observational clinical study designed to evaluate the efficacy and safety of Epunamin combined with a DECP-based regimen in patients with relapsed/refractory multiple myeloma (RRMM). A total of 48 eligible patients aged 18-75 years who meet the revised International Myeloma Working Group diagnostic criteria and have received at least one prior systemic therapy will be enrolled. Eligible participants must have an Eastern Cooperative Oncology Group performance status of 0-3 and provide written informed consent.

Major exclusion criteria include severe cardiac, pulmonary, hepatic, or renal dysfunction; unresolved toxicities from prior chemotherapy; grade ≥2 peripheral neuropathy; active severe infection; plasma cell leukemia; concurrent malignancies diagnosed within 2 years; HIV infection; pregnancy or lactation; and known hypersensitivity to study drugs.

Endpoints:

The primary endpoint is overall response rate (ORR) after completion of four treatment cycles. Secondary endpoints include very good partial response (VGPR), complete response (CR), stringent complete response (sCR), minimal residual disease (MRD), duration of response (DOR), and time to next treatment (TTNT), based on laboratory findings and revised IMWG criteria.

Statistical Analysis:

Continuous variables will be summarized using mean, median, standard deviation, minimum, and maximum values. Categorical variables will be presented as counts and percentages. Normally distributed continuous variables will be analyzed using Student's t-test or analysis of variance, while non-normally distributed variables will be compared using rank-sum tests. Categorical variables will be analyzed using the chi-square test or Fisher's exact test. Ordinal variables will be assessed using Ridit analysis or nonparametric rank-sum tests. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), will be estimated using the Kaplan-Meier method, with comparisons performed using the log-rank test. All statistical analyses will be two-sided, with P \< 0.05 considered statistically significant.

Study Period:

Patient enrollment and follow-up are planned from October 2025 to September 2027.

Первичные конечные точки

• Objective response rate (ORR) is defined as the proportion of evaluable patients who achieve complete response (CR) or partial response (PR) after treatment. [Срок оценки: At the end of cycle 4 (approximately 4 months) Description]

Критерии участия

Критерии включения

Adults aged 18 to 75 years with relapsed/refractory Multiple Myeloma diagnosed according to revised IMWG criteria.

Received at least one prior systemic treatment regimen. Eastern Cooperative Oncology Group Performance Status score of 0-3. Able to understand treatment-related changes and management options during therapy and follow-up, with good treatment adherence and follow-up compliance.

Provided written informed consent. -

Критерии исключения

Severe dysfunction of major organs, including cardiac, pulmonary, hepatic, or renal impairment, defined as left ventricular ejection fraction <50%, diffusion capacity for carbon monoxide <50% of predicted value due to chronic respiratory disease, serum bilirubin >2 mg/dL, alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of normal, or estimated glomerular filtration rate <30 mL/min.

Toxicities from prior chemotherapy not recovered to baseline or grade ≤1. Peripheral neuropathy grade ≥2, or grade 1 with pain. Major surgery, radiotherapy, infection requiring systemic antibiotic treatment, or other severe infection within 14 days before enrollment.

High-risk plasma cell leukemia with peripheral blood plasma cells ≥20%. Psychiatric disorders, cognitive impairment, or other conditions affecting self-control or study compliance.

Pregnant or breastfeeding women, or fertile patients unwilling to use adequate contraception during the study. Male patients unwilling to use effective contraception or refrain from sperm donation during treatment and for 3 months after the last dose.

Diagnosis or treatment of another malignancy within 2 years before enrollment. Known hypersensitivity to Epunamin, Dexamethasone, Cisplatin, Etoposide, or Cyclophosphamide.

Human Immunodeficiency Virus Infection positive. Participation in another clinical trial within 30 days before enrollment or during the study period.

Any condition considered unsuitable for participation by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• ShanxiBethuneH — Taiyuan

Публикации

• Gamie Z, Kapriniotis K, Papanikolaou D, Haagensen E, Da Conceicao Ribeiro R, Dalgarno K, Krippner-Heidenreich A, Gerrand C, Tsiridis E, Rankin KS. TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data. Cancer Lett. 2017 Nov 28;409:66-80. doi: 10.1016/j.canlet.2017.08.036. Epub 2017 Sep 6. PMID 28888998
• NCCN Guidelines Version 3.2024 Multiple Myeloma[M].2024
• Xia Z, Leng Y, Fang B, Liang Y, Li W, Fu C, Yang L, Ke X, Jiang H, Weng J, Liu L, Zhao Y, Zhang X, Huang Z, Liu A, Shi Q, Gao Y, Chen X, Pan L, Cai Z, Wang Z, Wang Y, Fan Y, Hou M, Ma Y, Hu J, Liu J, Zhou J, Zhang X, Meng H, Lu X, Li F, Ren H, Huang B, Shao Z, Zhou H, Hu Y, Yang S, Zheng X, Wei P, Pang H, Yu W, Liu Y, Gao S, Yan L, Ma Y, Jing H, Du J, Ling W, Zhang J, Sui W, Wang F, Li X, Chen W. PMID 37838670
• Globocan, The Global Cancer Observatory (GCO) (2020a) Cancer Today; World Fact Sheets. 2020.
• Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022 Aug;97(8):1086-1107. doi: 10.1002/ajh.26590. Epub 2022 May 23. PMID 35560063

Идентификаторы

NCT: NCT07497165 · IIT-2025-121-KS043

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗