Randomized Phase II Trial of CD3/CD28 Activated Id-KLH Primed Autologous Lymphocytes in Subjects With Myeloma Undergoing Autologous Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Participants With Id-specific Immunity
研究概览
简要总结
This study will enroll myeloma subjects undergoing autotransplantation. The primary objective of this study is to evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense Id-specific immunity than non Id-KLH primed CD3/CD28 activated autologous lymphocytes. There will be 2 arms in the study, one receiving a DLI with non Id-KLH vaccine and one receiving aDLI with Id-KLH vaccine.
详细描述
The primary objectives of this study is to evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense id-specific immunity than non id-KLH primed CD3/CD28 activated autologous lymphocytes. The secondary objectives of this study is to demonstrate that doses of 1 times 10e10 Id-KLH primed CD3/CD28 autologous lymphocytes can be infused safely and effectively in more than 80 percent of eligible patients, to determine whether Id-KLH primed CD3/CD28 activated autologous lymphocytes and to determine if the presence of Id-specific immunity correlates with disease response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •SCREEN #1 (Visit 1) Step 1:
- •Diagnosis of symptomatic multiple myeloma.
- •Less than 10 months after initiation of systemic therapy.
- •One or two lines of induction therapy with commonly used regimens.
- •Age greater than or equal to 18 years to less than or equal to 70 years at the time of enrollment.
- •IgG paraprotein (not of IgG3 subtype) with a paraprotein peak (M-spike) of ≥0.2 g/dL. Alternatively subjects who have previously stored purified Id-specific protein on other clinical or laboratory protocols.
- •Echocardiogram or MUGA with an ejection fraction of 45% or more and no uncompensated congestive heart failure or uncontrolled arrhythmias.
- •Adequate pulmonary function as defined by FEV1, FVC and actual or corrected DLCO of 50% or greater of the predicted value for age, sex and size.
- •Adequate renal function as defined by creatinine of 2.0 mg/dl or less or a creatinine clearance of 40cc/min or more.
- •Adequate hepatic function as defined by a total bilirubin of 2.0 mg/dl or less and AST and ALT less than 2 times upper limit of normal.
- •Ability to sign written informed consent.
- •Karnofsky performance status of at least 80% or more.
- •Negative serum Beta HCG test in women of child bearing potential and agree to use a medically acceptable form of birth control while on the study drugs.
- •Subjects with melphalan-based induction
- •Active uncontrolled infection
- •HIV+ or active hepatitis B or C as defined by positive viral load or serology.
- •Pre-existing autoimmune diseases, with exception of Hashimoto's thyroiditis.
- •Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during Tcell collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids is permitted as well.
- •Prior autologous or allogeneic transplant.
- •For this study, there will be no exceptions to eligibility granted.
- •4.2 PRE-VACCINE #1 ASSESSMENT (Visit 3) Step 2
- •Subjects must meet the following criteria to proceed with vaccination:
- •Less than 9 months from randomization.
- •Adequate renal function as defined by creatinine of 2.0 mg/dl or less or a creatinine clearance of 40cc/min or more.
- •Adequate hepatic function as defined by a total bilirubin of 2.0 mg/dl or less and AST and ALT less than 2 times upper limit of normal.
- •Karnofsky performance status of at least 80% or more.
- •At least 2 weeks from last chemotherapy.
- •Negative serum Beta HCG test in women of child bearing potential.
排除标准
- 未提供
结局指标
主要结局
Participants With Id-specific Immunity
时间窗: 180 DAYS
Evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense Id-specific immunity than non Id-KLH primed CD3/CD28 activated autologous lymphocytes. RNA was isolated from CD4 and CD8 T cells pre-vaccine, and at day 30, 90 and 180 post-vaccine for gene expression analysis. The Nanostring Human immunology V2 kit, a multiplex assay for 594 genes involved in the human immunology response, was used with an nCounter digital analyzer to quantify immune response gene expression levels. Subjects were considered to have Id-specific immunity if they induced expression of effector (TBX21, KLRG1) and memory (CCL5) associated genes in CD8 T cells in post-vaccine time-points compared to baseline.
次要结局
未报告次要终点