Efficacy of Sequential BCMA CAR-T Cell Therapy Following Autologous Hematopoietic Stem Cell Transplantation in Transplant-eligible Newly Diagnosed Multiple Myeloma (AUTO-CAR-T)

A Single-Center, Open-Label, Single-Arm Clinical Study of Sequential Anti-BCMA CAR-T Cell Therapy Following Autologous Hematopoietic Stem Cell Transplantation in Transplant-Eligible Newly Diagnosed Multiple Myeloma

1. Study Title A Single-Center, Open-Label, Single-Arm Clinical Study of Sequential Anti-BCMA CAR-T Cell Therapy Following Autologous Hematopoietic Stem Cell Transplantation in Transplant-Eligible Newly Diagnosed Multiple Myeloma
2. Study Objective This study aims to evaluate the safety and efficacy of sequential anti-BCMA CAR-T cell therapy following autologous hematopoietic stem cell transplantation (ASCT) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), in order to provide evidence for optimizing treatment strategies in this population.
3. Study Design This is a single-center, open-label, single-arm clinical study. A total of 50 patients with newly diagnosed multiple myeloma who meet the inclusion criteria will be enrolled. All participants will receive a standardized treatment regimen and undergo regular follow-up for efficacy and safety assessments.
4. Study Population and Eligibility Criteria (1) Inclusion Criteria Age between 18 and 70 years;

Estimated life expectancy > 12 weeks;

Diagnosis of multiple myeloma confirmed by physical examination, histopathology, laboratory tests, and imaging;

Liver function: ALT and AST < 3 times the upper limit of normal;

Karnofsky Performance Status (KPS) score > 50%;

No severe dysfunction of major organs such as the liver or heart;

Willingness to undergo ASCT and CAR-T cell therapy for multiple myeloma;

Ability to provide peripheral venous blood and no contraindications to leukapheresis;

Ability to understand the study and sign a written informed consent voluntarily.

(2) Exclusion Criteria Pregnant or lactating women, or those planning pregnancy within six months;

Patients with infectious diseases, including HIV infection or active tuberculosis;

Patients with active hepatitis B or C virus infection;

Pre-screening indicates peripheral blood T cell transduction efficiency <10% or expansion fold <5× under CD3/CD28 co-stimulation;

Patients with abnormal vital signs or unable to cooperate with the procedures;

Patients with psychiatric or psychological disorders that impair compliance or assessment;

Patients with a history of severe allergies or hypersensitivity, particularly to interleukin-2 (IL-2);

Patients with systemic or severe local infections requiring anti-infective therapy;

Patients with significant dysfunction of vital organs such as the heart, lungs, or brain;

Any other condition deemed unsuitable for participation by the investigator.

5. Treatment Protocol All enrolled patients will receive three cycles of induction therapy using either the DVRd regimen (Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone) or the DKRd regimen (Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone).

Following induction, patients will undergo high-dose melphalan conditioning followed by autologous hematopoietic stem cell transplantation. On Day 5 after stem cell reinfusion, patients will receive anti-BCMA CAR-T cell infusion.

After CAR-T therapy, patients will enter the maintenance phase with lenalidomide monotherapy or lenalidomide in combination with bortezomib until disease progression or intolerable toxicity occurs.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kailin Xu; Phone Number: 15162166166; Email: lihmd@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Age between 18 and 70 years; Estimated life expectancy > 12 weeks; Diagnosis of multiple myeloma confirmed by physical examination, histopathology, laboratory tests, and imaging; Liver function: ALT and AST < 3 times the upper limit of normal; Karnofsky Performance Status (KPS) score > 50%; No severe dysfunction of major organs such as the liver or heart; Willingness to undergo ASCT and CAR-T cell therapy for multiple myeloma; Ability to provide peripheral venous blood and no contraindications to leukapheresis; Ability to understand the study and sign a written informed consent voluntarily.

Exclusion Criteria:

Pregnant or lactating women, or those planning pregnancy within six months; Patients with infectious diseases, including HIV infection or active tuberculosis; Patients with active hepatitis B or C virus infection; Pre-screening indicates peripheral blood T cell transduction efficiency <10% or expansion fold <5× under CD3/CD28 co-stimulation; Patients with abnormal vital signs or unable to cooperate with the procedures; Patients with psychiatric or psychological disorders that impair compliance or assessment; Patients with a history of severe allergies or hypersensitivity, particularly to interleukin-2 (IL-2); Patients with systemic or severe local infections requiring anti-infective therapy; Patients with significant dysfunction of vital organs such as the heart, lungs, or brain; Any other condition deemed unsuitable for participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR-T following ASCT; All enrolled patients will receive three cycles of induction therapy using either the DVRd regimen (Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone) or the DKRd regimen (Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone). Following induction, patients will undergo high-dose melphalan conditioning followed by autologous hematopoietic stem cell transplantation. On Day 5 after stem cell reinfusion, patients will receive anti-BCMA CAR-T cell infusion. After CAR-T therapy, patients will enter the maintenance phase with lenalidomide monotherapy or lenalidomide in combination with bortezomib until disease progression or intolerable toxicity occurs.

Biological: CAR-T; All enrolled patients will receive three cycles of induction therapy using either the DVRd regimen (Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone) or the DKRd regimen (Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone). Following induction, patients will undergo high-dose melphalan conditioning followed by autologous hematopoietic stem cell transplantation. On Day 5 after stem cell reinfusion, patients will receive anti-BCMA CAR-T cell infusion. After CAR-T therapy, patients will enter the maintenance phase with lenalidomide monotherapy or lenalidomide in combination with bortezomib until disease progression or intolerable toxicity occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The proportion of patients achieving partial response (PR) or better according to the IMWG criteria.	Month 6, 12, 18 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from CAR-T infusion to disease progression or death from any cause.	Month 6, 12, 18 and 24
Overall Survival (OS)	Time from CAR-T infusion to death from any cause.	Month 6, 12, 18 and 24

Collaborators and Investigators

• Sponsor: Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: March 29, 2025
• First Submitted That Met QC Criteria: March 29, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: March 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: XYFY2025-KL063-01 (Other Identifier: The Affiliated Hospital oh Xuzhou Medical University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No