Epunamin Combined With DECP for Relapsed/Refractory Multiple Myeloma

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Relapsed/Refractory Multiple Myeloma (RRMM)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 48

Contacts and Locations

• Study Contact: Name: Tian Weiwei Tian Weiwei, PhD; Phone Number: +156-13485304136; Email: tianweiwei@yesh.net

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Recruiting
      • ShanxiBethuneH
      • Contact: Tian Weiwei Tian Weiwei, PhD; Phone Number: +156-13485304136; Email: tianweiwei@yesh.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

relapsed/refractory Multiple Myeloma

Description

Inclusion Criteria:

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. -

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients Receiving Epunamin Combined With DECP-Based Regimen; Patients with relapsed/refractory Multiple Myeloma will receive Epunamin in combination with a DECP-based regimen as follows: Epunamin 10 mg/kg administered on days 1-5, or days 1-3 and days 15-17 Cisplatin 10 mg/m² on days 1-4 Etoposide 40 mg/m² on days 1-4 Cyclophosphamide 300 mg/m² on days 1-4 Dexamethasone 20-40 mg on days 1-4 Each treatment cycle lasts 28 days. Patients achieving clinical benefit will receive at least 4-6 cycles of treatment. For first administration, Epunamin will be introduced using a step-up dosing strategy, particularly in patients with high tumor burden or extramedullary bulky disease. The DECP regimen will start at 1/2 to 2/3 of the standard dose, and in patients older than 70 years, treatment will begin at 1/2 dose.During treatment, thromboprophylaxis with low-molecular-weight heparin or Rivaroxaban will be administered to prevent thrombotic events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) is defined as the proportion of evaluable patients who achieve complete response (CR) or partial response (PR) after treatment.	Formal efficacy evaluation will be performed at the end of cycle 4. M-protein and related laboratory parameters will be monitored during each treatment cycle, while bone marrow examination and serum free light chain assessment will be performed every 2 cycles to evaluate depth of response.	At the end of cycle 4 (approximately 4 months) Description

Collaborators and Investigators

• Sponsor: Shanxi Bethune Hospital

Publications and helpful links

General Publications

• 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.
• NCCN Guidelines Version 3.2024 Multiple Myeloma[M].2024
• Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (Apo-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial. BMC Cancer. 2023 Oct 14;23(1):980.
• Globocan, The Global Cancer Observatory (GCO) (2020a) Cancer Today; World Fact Sheets. 2020.
• [1]Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. American journal of hematology, 2022: p. 1-22.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Epunamin; DECP-Based Regimen
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: IIT-2025-121-KS043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD sharing is not planned because the collected data contain sensitive clinical information, and data access is restricted in accordance with institutional policies and patient confidentiality requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No