Clinical trial NCT06913192: Efficacy of Sequential BCMA CAR-T Cell Therapy Following Autologous Hematopoietic Stem Cell Transplantation in Transplant-eligible Newly Diagnosed Multiple Myeloma
Official 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Xuzhou Medical University
Sponsor class: OTHER
First posted: 2025-04-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Month 6, 12, 18 and 24
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Month 6, 12, 18 and 24
measure: Overall Survival (OS)
timeFrame: Month 6, 12, 18 and 24
Other outcomes:
Locations:
Study officials:
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