A Phase I/II Clinical Study of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Equecabtagene Autoleucel) for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 17
- 试验地点
- 3
- 主要终点
- Safety endpoint (Part 1)- Adverse Event（AEs）
研究概览
简要总结
This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Equecabtagene Autoleucel) in subjects with relapsed and refractory Multiple Myeloma.
详细描述
This study is divided into two stages: Part 1 and Part 2. Part 1: For exploratory research purposes, no more than 3 subjects will be enrolled at an exploratory dose.
Part 2: The purpose of this phase is to explore the efficacy of Equecabtagene Autoleucel (Eque-cel) as a last-line treatment for RRMM and further confirm its safety.
In this Study，Leukapheresis procedure will be performed to manufacture Eque-cel modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide is performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of Eque-cel at 1.0 x 10^6 CAR+ T cells/Kg or 0.5 x 10^6 CAR+ T cells/Kg（if all three subjects in Part 1 experience the Toxicity Requiring Dose Reduction）. Subjects will be followed in the study for a minimum of 2 years after Eque-cel infusion.
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
- •Inclusion Criteria
- •1. Aged 18 to 70 years, male or female.
- •2. Patients with a confirmed diagnosis of relapsed/refractory multiple myeloma according to the IMWG diagnostic criteria.
- •3. Patients who have received at least three prior treatment regimens (including proteasome inhibitors, immunomodulatory agents, and anti-CD38 antibody-based chemotherapy regimens) and have documented disease progression during or within 12 months of their most recent anti-myeloma treatment.
- •4. Patients with measurable disease at screening, as determined by any of the following criteria:
- •Serum M-protein level: IgG type M-protein level ≥ 10 g/L, IgA, IgD, IgE, IgM type M-protein level ≥ 5 g/L
- •Urinary M-protein level ≥ 200 mg/24 hours
- •5. Light-chain multiple myeloma without measurable M protein in serum or urine: involved serum free light chain ≥ 100 mg/L with an abnormal serum κ/λ free light chain ratio. ECOG PS 0 or
- •6. Patients must have adequate organ function and meet all of the following pre-enrollment laboratory test results:
- •Hematological Tests:
- •Absolute Neutrophil Count (ANC) ≥ 1×109/L (Supportive growth factors are permitted, but supportive treatment must not have been administered within 7 days prior to the laboratory test)
- •Absolute Lymphocyte Count (ALC) ≥ 0.3×109/L
- •Platelet Count ≥ 50×109/L (Supportive transfusions must not have been administered within 7 days prior to the laboratory test)
- •Hemoglobin ≥ 60 g/L (Red blood cell [RBC] transfusions must not have been administered within 7 days prior to the laboratory test, but recombinant human erythropoietin is permitted)
- •Liver Function:
- •ALT and AST ≤ 2.5×upper limit of normal (ULN)
- •Serum Total Bilirubin ≤ 1.5 x ULN Renal Function: Creatinine clearance (CrCl) calculated using the Cockcroft-Gault formula ≥ 40 mL/min CrCl = (140 - age) × weight (kg) × [0.85 for women] / 72 × [ serum creatinine (mg/dL)]
- •Coagulation function:
- •Fibrinogen ≥ 1.0 g/L
- •Activated partial thromboplastin time (APTT) ≤ 1.5× ULN
- •Prothrombin time (PT) ≤ 1.5× ULN Corrected serum calcium ≤11 mg/dL Oxygen saturation > 91% Left ventricular ejection fraction (LVEF) ≥ 50%.
- •7. Female patients of childbearing potential or male patients with partners of childbearing potential agree to use effective contraception (safe-day contraception not included) throughout the study period from screening through one year after Eque-cel infusion.
- •"Effective contraceptive methods" specifically refers to: User-independent methods: 1) Intrauterine devices, intrauterine hormone-releasing systems; 2) Partner has undergone vasectomy.
- •User-dependent methods: 1) Combined hormonal contraception (containing estrogen and progestin) with ovulation suppression:
- •Oral; 2) Progestin-only hormonal contraception with ovulation suppression ( oral).
- •Prior to screening, subjects must manually sign an Institutional Review Board-approved ICF.
排除标准
- •1. Patients with graft-versus-host disease (GVHD) or requiring long-term use of immunosuppressants.
- •2. Patients with a history of BCMA-targeted therapy.
- •3. Patients who have undergone autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks prior to apheresis, two auto-HSCTs, or prior allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- •4. Patients who have received prior anti-myeloma therapy, including:
- •Monoclonal antibody therapy within 21 days prior to apheresis.
- •Cytotoxic chemotherapy or proteasome inhibitor therapy within 14 days prior to apheresis.
- •Immunomodulatory therapy within 7 days prior to apheresis.
- •Other anti-myeloma therapy within 14 days or within 5 half-lives (whichever is longer) prior to apheresis.
- •5. Use of systemic corticosteroids at a therapeutic dose (defined as >20 mg/day of prednisone or equivalent) within 7 days prior to apheresis.
- •Physiological replacement steroids, topical steroids, and inhaled steroids are permitted.
- •6. Patients with uncontrolled hypertension despite medical therapy.
- •7. Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] grade ≥ III), and severe arrhythmia.
- •8. Unstable systemic disease as determined by the investigator, including but not limited to severe liver, renal, or metabolic disease requiring treatment.
- •9. Patients with malignancies other than multiple myeloma (MM) within 5 years prior to screening.
- •excluding adequately treated cervical epithelial cell adenocarcinoma, basal cell carcinoma or squamous cell skin cancer, localized prostate cancer after curative surgery, and ductal carcinoma in situ after curative surgery.
- •10. Patients with a history of solid organ transplantation.
- •11. Patients with suspected or confirmed central nervous system infiltration by plasma cell neoplasms.
- •12. Multiple myeloma patients with extramedullary lesions (excluding those with only paraskeletal extramedullary lesions where the single largest transverse diameter is ≤3cm).
- •13. Multiple myeloma patients with concomitant plasma cell leukemia (peripheral blood plasma cell count ≥5%).
- •14. Major surgery within 2 weeks prior to apheresis or planned surgery within 2 weeks after study treatment (subjects scheduled for local anesthesia surgery may participate in this study).
- •15. Received investigational drugs from other interventional clinical trials within 1 month prior to signing the Informed Consent Form (ICF).
- •16. Patients with an uncontrolled active infection (excluding CTCAE Grade 2 urinary tract infection or respiratory infection) within 7 days prior to apheresis.
- •17. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with detectable hepatitis B virus (HBV) DNA in peripheral blood; Hepatitis C virus (HCV) positive with hepatitis C virus (HCV) RNA positive in peripheral blood; Human Immunodeficiency Virus (HIV) antibody positive; Cytomegalovirus (CMV) DNA test positive; Syphilis test positive.
- •18. Pregnant or lactating women.
- •19. Patients with psychiatric disorders, impaired consciousness, or central nervous system disease.
- •20. Patients whose non-hematologic toxicities from previous antimyeloma therapy have not resolved to baseline or Grade ≤ 1 (NCI-CTCAE v5.0) (excluding alopecia and Grade 2 peripheral neuropathy).
- •21. Other conditions deemed ineligible for enrollment by the investigator.
研究组 & 干预措施
Eque-cel in relapsed and refractory multiple myeloma patients
Eque-cel will be infused at 1.0 x 10^6 CAR+ T cells or 0.5 x 10^6 CAR+ T cells/Kg（if all three subjects in Part 1 experience the Toxicity Requiring Dose Reduction）after receiving lymphodepleting chemotherapy.
干预措施: Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Eque-cel) (Drug)
结局指标
主要结局
Safety endpoint (Part 1)- Adverse Event（AEs）
时间窗: up to 2 years from Eque-cel infusion
Incidence and severity of adverse events as assessed by NCI-CTCAE v5.0 (except CRS and ICANS assessed according to the criteria of 2019 ASTCT criteria).
Safety endpoint (Part 1)-CRS
时间窗: up to 2 years from Eque-cel infusion
Incidence and severity of cytokine release syndrome (CRS； based on the 2019 ASTCT criteria）
Safety endpoint (Part 1)-ICANS
时间窗: up to 2 years from Eque-cel infusion
Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS).( based on the 2019 ASTCT criteria)
Efficacy endpoint (Part 2): Independent Review Committee (IRC)-assessed ORR
时间窗: up to 2 years from Eque-cel infusion
Rate of best response (PR, very good PR, CR, sCR) after Eque-cel infusion in all subjects at the time the last subject completed the 6-month follow-up.
次要结局
- Safety endpoint (Part 2)- Adverse Event（AEs）(up to 2 years from Eque-cel infusion)
- Efficacy endpoint -Investigator-assessed overall response rate (ORR)(up to 2 years from Eque-cel infusion)
- Efficacy endpoint -IRC- and investigator-assessed ORR(up to 2 years from Eque-cel infusion)
- Efficacy endpoint -IRC and investigator-assessed duration of response (DOR)(up to 2 years from Eque-cel infusion)
- IRC and investigator-assessed time to response (TTR)(up to 2 years from Eque-cel infusion)
- IRC and investigator-assessed time to complete response (TTCR)(up to 2 years from Eque-cel infusion)
- Minimal residual disease (MRD) assessment by flow cytometry(up to 2 years from Eque-cel infusion)
- IRC and investigator-assessed progression-free survival (PFS)(up to 2 years from Eque-cel infusion)
- Overall survival (OS)(up to 2 years from Eque-cel infusion)
- Pharmacokinetic Endpoint-Cmax(up to 2 years from Eque-cel infusion)
- Pharmacokinetic Endpoint-Tmax(up to 2 years from Eque-cel infusion)
- Pharmacokinetic Endpoint-AUC(up to 2 years from Eque-cel infusion)
- - Pharmacokinetic Endpoint-AUC(up to 2 years from Eque-cel infusion)
- Pharmacodynamic Endpoint-sBCMA(up to 2 years from Eque-cel infusion)
- Pharmacodynamic Endpoint-C-reactive protein (CRP)(up to 2 years from Eque-cel infusion)
- Pharmacodynamic Endpoint -Ferritin(up to 2 years from Eque-cel infusion)
- Pharmacodynamic Endpoint -Interleukin-6 (IL-6)(up to 2 years from Eque-cel infusion)