Phase I/II Study of Anti-CD3 x Anti-SLAMF7 (Anti-CS-1) Bispecific Antibody Armed Fresh Peripheral Blood Mononuclear Cells (SLAMF7 FPBMC) in Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to understand the safety and estimate the efficacy of combining anti-CD3 x anti-SLAMF7 bispecific antibody fresh peripheral blood mononuclear cells (SLAMF7 FPBMC/CS1 FPBMC) for patients with relapsed and/or refractory multiple myeloma. Patients receive 8 weekly doses and then 8 more doses every 2 weeks of SLAMF7 FPBMC by intravenous infusion.
详细描述
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure. The white blood cells, specifically T cells, are then mixed with two proteins, OKT3 and IL-2, which activate the cells to multiply.
The "activated" T cells are coated with the OKT3 and elotuzumab (an anti-SLAMF7 drug) to produce bispecific fresh peripheral blood mononuclear cells (FPBMC).
About 72 hours after the leukapheresis procedure, SLAMF7 FPBMC infusions will start. After about 8-9 weeks, participants will have another leukapheresis procedure and then receive doses every 2 weeks for 8 more doses. Before, throughout and following SLAMF7 FPBMC, research blood will be collected to better understand immune response. Disease status will be checked regularly during and after study treatment.
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
- •Must have received ≥ 2 consecutive cycles of treatment which include an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody either used individually or in combination
- •Documented refractory or relapsed myeloma
- •Refractory is defined as progression while on treatment or within 60 days of last treatment
- •Measurable disease based on at least one of the following lab results within 28 days of enrollment
- •Serum IgG, IgA, or IgM M-protein ≥ 1.0 g/dL
- •Urine M-protein ≥ 200 mg excreted in a 24-hr collection sample
- •Involved serum free light chain (FLC) ≥ 100 mg/L provided the FLC ratio is abnormal
- •ECOG Performance Status 0 -2
- •Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or Echocardiogram)
- •Age ≥ 18 years at the time of consent (Written informed consent and HIPAA authorization for release of personal health information)
- •Females of childbearing potential, and males, must be willing to use an effective method of contraception for the duration of the treatment with study drug plus 90 days (duration of sperm turnover).
- •Adequate cardiac function as defined as:
- •No EKG evidence of acute ischemia
- •No EKG evidence of clinically significant conduction system abnormalities in the opinion of the treating investigator
- •No EKG evidence of > Grade 2 (> 480 ms) QTc prolongation
- •No uncontrolled angina or severe ventricular arrhythmias
- •No clinically significant pericardial disease
- •No history of myocardial infarction (MI) in the last 6 months
- •No Class 3 or higher New York Heart Association Congestive Heart Failure
- •Demonstrate adequate organ function as defined below; all screening labs should be performed within 14 days prior to enrollment.
- •Absolute lymphocyte count ≥ 400/mm3
- •Absolute neutrophil count ≥ 1,000/mm3
- •Platelets ≥ 75,000/mm3
- •Calculated Creatinine Clearance ≥ 30 ml/min
- •Serum total bilirubin ≤ 1.5 x upper limit of normal
- •AST and ALT < 2.5 times normal
排除标准
- •Known hypersensitivity to elotuzumab (Elo)
- •Amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome, or known central nervous system (CNS) involvement
- •Receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- •NOTE: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Active autoimmune disease that has required systemic treatment in the past 2 years before enrollment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment
- •Active liver disease (such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis)
- •HIV positive or known active Hepatitis C (e.g., HCV RNA [qualitative] is detected) or Hepatitis B (e.g. HBsAg reactive) virus
- •Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
- •Has an active infection requiring systemic therapy
- •History of active TB (Bacillus Tuberculosis)
- •Has received a live vaccine within 30 days of enrollment.
- •Anti-myeloma drug therapy (including radiation therapy) ≤ 14 days prior to apheresis
- •History of myocardial infarction (within 6 months of enrollment), stable or unstable angina
- •History of another malignancy within the past 3 years before enrollment. -- Exceptions include:
- •Basal cell carcinoma of the skin or squamous cell carcinoma of the skin,
- •In situ cancers that have undergone potentially curative therapy
- •Prisoners or patients who are incarcerated
- •Patients who are compulsorily detained for treatment of either a psychiatric or physical illness
- •Pregnant or breastfeeding females: Females of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
研究组 & 干预措施
SLAMF7 FPBMC
Participants will undergo apheresis to collect cells to make SLAMF7 fresh peripheral blood mononuclear cells (FPBMC). These cells will be activated in the lab to fight against multiple myeloma. About 3-4 days after apheresis, participants will start receiving infusions of SLAMF7 FPBMC. Throughout treatment, participants will have blood taken for labs, to check disease status and also to look at immune response. Study treatment will stop if the participant has disease progression.
干预措施: SLAMF7 FPBMC (Drug)
结局指标
主要结局
Dose-limiting toxicities (DLTs)
时间窗: From time of informed consent through one week following 8th FPBMC infusion
An adverse event that is considered at least possibly related to SLAMF7 FPBMC and meets at least one of the protocol-defined criteria
Adverse event profile
时间窗: From time of informed consent through 30 days following last FPBMC infusion
Severity, frequency, category, seriousness and duration of adverse events
次要结局
- Overall Survival (OS)(Through 3 years after first FPBMC infusion)
- Overall response rate (ORR)(About once a month during study treatment (for about 6 months), then about every 3 months for 3 years or until first progression)
- Minimal Residual Disease (MRD) status(Through first progression of disease (maximum of 3 years from first infusion))
- Cellular anti-myeloma responses(Multiple timepoints through 12 months after last FPBMC infusion)
- Progression-free survival (PFS)(From informed consent through first progression or 3 years after enrollment)
- Humoral anti-myeloma responses(Multiple timepoints through 12 months after last FPBMC infusion)
- Lymphocyte response following infusions of SLAMF7 FPBMC(Blood samples collected prior to first infusion and then before the second through fifth infusions)
研究者
Laahn Foster
Associate Progessor
University of Virginia