A Prospective, Single-Arm, Phase II Study of Autologous Stem Cell Transplantation Combined With BCMA CAR-T Therapy Followed by GPRC5D/CD3 Bispecific Antibody Maintenance in Transplant-Eligible Patients With Ultra-High-Risk Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Sustained MRD-negative rate
研究概览
简要总结
This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of autologous stem cell transplantation combined with BCMA CAR-T therapy followed by GPRC5D/CD3 bispecific antibody maintenance in transplant-eligible patients with ultra-high-risk multiple myeloma.
详细描述
All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled. Enrolled patients will undergo autologous stem cell transplantation (ASCT) combined with BCMA CAR-T cell therapy, followed by GPRC5D/CD3 bispecific antibody therapy.
Patients who achieve a stringent complete response (sCR) and sustained MRD negativity (≥12 months) will receive maintenance therapy for 24 months, and may then enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response during observation will resume maintenance therapy.
Patients who do not achieve both sCR and sustained MRD negativity (≥12 months) will continue GPRC5D/CD3 bispecific antibody therapy until disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and ≤ 70 years.
- •Participants with documented newly-diagnosed multiple myeloma according to IMWG diagnostic criteria.
- •Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
- •Patients deemed eligible for high-dose chemotherapy with ASCT.
- •Presence of at least one of the following ultra-high-risk features: a. Double-hit multiple myeloma, defined as the presence of at least two of the following high-risk cytogenetic abnormalities: t(4;14), t(14;16), deletion 1p, gain 1q, MYC rearrangement, deletion 17p, or TP53 mutation; b. Presence of extramedullary soft tissue plasmacytomas; c. Circulating plasma cells ≥2% in peripheral blood.
- •Tumor cells were BCMA and GPRC5D positive.
- •Serum total bilirubin <2 x upper limit of normal (ULN), serum AST and ALT <3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
- •Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.
排除标准
- •Active amyloidosis.
- •Central nervous system involvement.
- •Prior BCMA-targeted therapy or CAR-T therapy.
- •Active hepatitis B or hepatitis C virus infection.
- •Known HIV infection.
- •Life expectancy <6 months.
- •Woman who are pregnant or breastfeeding.
- •Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.
- •Any other conditions that are not eligible for the trial in the judgement of the principal investigator.
研究组 & 干预措施
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance
Patients will undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance
Patients will undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.
干预措施: BCMA CAR-T (Biological)
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance
Patients will undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.
干预措施: GPRC5D/CD3 BiTEs (Drug)
结局指标
主要结局
Sustained MRD-negative rate
时间窗: Up to 2 year
Rate of patients achieving sustained MRD negativity for more than 12 months
MRD negativity rate
时间窗: Up to 2 years
Rate of patients achieving MRD negativity
次要结局
- Safety and Tolerability(Up to 2 year)
- Complete response rate (CRR)(Up to 2 years)
- Progression free survival (PFS)(Up to 3 year)
- Overall survival (OS)(Up to 5 year)