NCT05411497进行中（未招募）1 期
Use of Natural Signals and Ambient Dendritic Cells to Culture-Expand Cancer Targeting T-Cells Directly From Unfractionated Peripheral Blood: A Phase 1 T-Cell Dose Escalation Trial Targeting Relapsed and Refractory MUC1-Expressing Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Mayo Clinic
- 入组人数
- 5
- 试验地点
- 4
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory) and is positive for expression of the MUC1 protein. T-cells are infection fighting blood cells that can kill cancer cells. MUC1-activated T-cells are made from the body's own T cells. The manufactured T-cells are made to target the MUC1 genetic marker and may help the body's immune system identify and kill cancer cells.
详细描述
PRIMARY OBJECTIVE:
I. To determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing multiple myeloma.
SECONDARY OBJECTIVES:
I. Obtain preliminary efficacy associated with MUC1-targeting peripheral blood mononuclear cells (PBMC) derived T cells in conjunction with cyclophosphamide (CTX) in MUC1-expressing multiple myeloma patients.
Ia. Assess best objective response observed based on International Myeloma Working Group (IMWG) criteria and duration of any partial or complete responses (partial response [PR] or complete response [CR]).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •MUC1 expression in multiple myeloma tumor cells verified by immunohistochemistry (IHC) or flow cytometry (FCM). Heterogeneous tumor expression of MUC1 is acceptable
- •Relapsed or refractory multiple myeloma previously treated with or intolerant to at least three prior lines of therapy and be relapsed or intolerant to a proteasome inhibitor, an immune modulatory drug (IMiD), and a CD38 antibody. Patients must be at least 90 days since an autologous stem cell transplant, if performed
- •Patients must have measurable disease per IMWG criteria on study entry, which must include at least one of the following:
- •Serum M-spike >= 0.5 g/dL Patients with IgA, IgM or IgD myeloma in whom serum protein electrophoresis is deemed unreliable for routine M-protein quantitation may be considered eligible if total serum IgA, IgM or IgD level is elevated above normal range and parallels disease course
- •24-hour urine M-spike >= 200 mg
- •Involved serum free light chain (FLC) >= 10 mg/L with an abnormal free light chain ratio
- •Bone marrow plasma cells > 30%
- •Patients with extramedullary disease:
- •1 lesion that has a single diameter of >= 2 cm measured by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT
- •Skin lesions can be used if the area is >= 2cm in at least one diameter and measured with a ruler
- •Willingness and ability to provide written informed consent
- •Willing to return to Mayo Clinic Hospital in Arizona (MCA) for follow-up during the active monitoring phase of the study
- •Willingness to provide mandatory blood, bone marrow biopsy, and aspirate specimens for correlative research
- •Willing to undergo leukapheresis for blood component collection
- •Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of study registration)
- •Lymphocyte count >= 500/mm^3 (within 14 days of study registration)
- •Hemoglobin >= 8.0 g/dL (within 14 days of study registration)
- •Platelet count >= 30,000/mm^3 (within 14 days of study registration)
- •Total bilirubin =< 2.0 mg/dL unless patient has documented Gilbert's syndrome (Subjects with Gilbert's Syndrome may be included if their total Bilirubin is =< 3.0 x upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN) (within 14 days of study registration)
- •Alanine aminotransferase (ALT) and aspartate amino transferase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement of their cancer) (within 14 days of study registration)
- •Prothrombin time, international normalized ratio (PT, INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulation therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding and no recent deep vein thrombosis [DVT]/pulmonary embolism [PE] within the last 6 months of enrollment)
- •Calculated creatinine clearance >= 30 ml/min using the Cockcroft-Gault formula (within 14 days of study registration)
- •Baseline oxygen saturation >= 90% on room air
排除标准
- •Clinically unresolved central nervous system (CNS) metastases
- •Prior treatment targeting MUC1
- •Subjects with known plasma cell leukemia (PCL)
- •Any of the following are excluded because this study involves an agent (CTX) that has known genotoxic, mutagenic and/or teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential who are unwilling to employ adequate birth control measures
- •History of myocardial infarction >= 6 months prior to registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias.
- •Failure to recover to grade 1 or baseline from acute, reversible effects of prior therapy regardless of interval since last treatment.
- •EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment.
- •Uncontrolled concurrent illness including, but not limited to:
- •Inability to clear an ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Uncontrolled psychiatric problems and/or difficult social situation
- •Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- •Any other conditions that the protocol investigators deem could potentially limit compliance with study requirements
- •Evidence of clinical immunocompromise and/or human immunodeficiency virus (HIV) positivity and currently receiving antiretroviral therapy
- •Patients requiring chronic supraphysiologic daily doses of steroids (>10 mg prednisone or prednisolone, >= 4 mg Decadron or >= 50 mg hydrocortisol daily)
- •Patients receiving any other investigational agent which could be considered a treatment for the neoplasm
- •Other active malignancy first documented =< 4 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of other malignancy, the patient must not be receiving other treatment aimed at suppressing its recurrence.
研究组 & 干预措施
Treatment (cyclophosphamide, MUC1-activated T-cells)
Experimental
LD CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes on days -5, -4, -3.
ASCT: Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0.
干预措施: Autologous MUC1-activated T-cells (Biological)
Treatment (cyclophosphamide, MUC1-activated T-cells)
Experimental
LD CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes on days -5, -4, -3.
ASCT: Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 4 years
次要结局
- Overall survival(From registration to death due to any cause, assessed up to 4 years)
- Clinical response(Up to 4 years)
- Progression-free survival(From registration to disease progression or death due to any cause, assessed up to 4 years)
研究者
研究点 (4)
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