Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
The purpose of this study is to determine whether the administration of highly effective "killer" cells (cytotoxic T cells), along with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF) immediately following Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) will enhance anti-tumor immune reconstitution and improve outcome of Multiple Myeloma patients.
The overall hypothesis of this proposal is that immediately following APBSCT the immune reconstitution is optimal to administer "killer" cells, combined with the administration of IL-2 and GM-CSF.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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New Hampshire
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Lebanon、New Hampshire、美国、03756
- Dartmouth-Hitchcock Medical Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Multiple Myeloma:
- Patients must meet criteria for diagnosis of Multiple Myeloma.
Patient must meet either criterion listed below:
- Stage I, II, or III newly diagnosed multiple myeloma
- Progressive or relapsed disease in partial response (PR) or complete response (CR)
- Primary refractory disease.
- Relapsed refractory disease.
- Patients may have received a prior autologous transplant.
- The patients must have recovered from all serious and life threatening effects of previous treatment at the time of study entry (unless this abnormality is believed to be due to the underlying myeloma).
- The patient must have adequate bone marrow function, i.e. a total white blood cell count (WBC) of > 2,000/ul, a Hemoglobin (Hgb) of > 7 gm/dl, and a platelet count of > 50,000/ul, unless this abnormality is believed to be due to the underlying myeloma.
- The patient must have adequate liver function, i.e. bilirubin <2.0 mg/dl, aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) not greater than 2 times the upper normal limit (unless this abnormality is believed to be due to the underlying myeloma).
- The patient must have adequate renal function, i.e. serum creatinine < 3.0 mg/dl, and/or creatinine clearance >50 ml/min. This eligibility criterion is excluded if renal insufficiency is believed to be secondary to myeloma.
- Age >18 years and < 75 years old
- The patient must have a Karnofsky status > 80%
- Patients must have a life expectancy of at least 12 weeks
- Left ventricular ejection fraction of > 45% by radionuclide scan or echocardiography
- Pulmonary function tests: forced vital capacity, Diffusing capacity of the lungs for carbon monoxide (DLCO) and expiratory volume in one second (FEV1) must be > 50% of predicted
- No significant co-morbid medical or psychiatric illness which would significantly compromise the patient's clinical care and chances of survival.
- Informed written consent must be obtained. Patients must be able to give informed consent as a prerequisite to this procedure. The Informed Consent form will become part of his/her permanent record and a copy will be given to the patient
Exclusion Criteria:
- Medical, social, or psychological factors which would prevent the patient from receiving or cooperating with the full course of therapy.
- Evidence on physical exam, lumbar puncture, computed tomography (CT), or magnetic resonance imaging (MRI) scan of central nervous system (CNS) involvement with malignancy
- Any clinically significant cardiac disease (angina, myocardial infarction, congestive heart failure, ventricular arrhythmias requiring therapy) or clinically significant obstructive/restrictive pulmonary disease
- Serology positive for human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLVI)
- Active hepatitis B or C
- History of seizures
- Concurrent or expected need for therapy with corticosteroids
- Active connective tissue disease
- Current "clinically significant" pleural effusion, pericardial effusion, or ascites
- Positive pregnancy test or presence of lactation
- Collection of fewer than 1 x 106 cluster of differentiation 34 positive (CD34+) cells/kg (peripheral blood stem cells). If the apheresis collection is inadequate based on this criteria, the patient will be removed from protocol and a marrow harvest may be performed
- A history of a second malignancy (other then squamous cell/ basal cell carcinoma of the skin or cervical dysplasia) must be reviewed by the Principal Investigator, before inclusion or exclusion in the study. Based upon the PI's review, this patient may be eligible (i.e., distant past history of a malignancy)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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其他:Ex-vivo expanded effector cells
Infusing IL-2 and GM-CSF post-Hematopoietic Stem Cell Transplant (HSCT)
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This trial will test if the combination of infusing ex vivo expanded cytotoxic effector cells with IL-2 and GM-CSF post-transplant will accelerate immune reconstitution, resulting in an effector cell-versus-myeloma effect and, possibly, improved clinical outcomes.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of Participants With Adverse Events in All Subjects
大体时间:From initiation of treatment on protocol until Day 100
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To establish the safety (toxicity) of myeloma patients treated with high dose melphalan, autologous peripheral blood stem cell transplantation (APBSCT) & adoptive transfer of cytotoxic effector cells with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF).
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From initiation of treatment on protocol until Day 100
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
大体时间:Day 15 post-transplant and between days 21 to 28 post-transplant
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To demonstrate that the effector cell infusions result in a clinical effect, phenotypic analyses of blood samples using flow cytometry will be performed prior to, and after each infusion, focusing on the CD8 + populations (CD3+CD8+, CD8+CD56+). As a complement to flow cytometry, the following assays will be used to identify cell subset precursor frequencies, subset proliferation, and cytokine production:
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Day 15 post-transplant and between days 21 to 28 post-transplant
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Time to Recovery of Absolute Neutrophil Count
大体时间:From initiation of treatment on protocol until Day 100
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To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
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From initiation of treatment on protocol until Day 100
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Time to Recovery of Platelet Count
大体时间:From initiation of treatment on protocol until Day 100
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To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
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From initiation of treatment on protocol until Day 100
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Assessment of Disease Response to Treatment
大体时间:From initiation of treatment on protocol until Day 100
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To establish the disease response of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
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From initiation of treatment on protocol until Day 100
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Number of Participants With Increased Expression of DAP10 and NKG2D on the CD8 Cell Population
大体时间:Pre-transplant and following the third and fourth cellular infusions
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After isolating CD8+ cells from patient's blood samples using the AutoMACS, we will evaluate the expression of NKG2D and DAP10 on all CD8+ cells (CD3+CD8+ and CD8+CD56+cells) pre-transplant (Baseline) and following the third and fourth cellular infusions using phenotypic analysis. We postulate the increased expression of both DAP10 and NKG2D on the CD8 population immediately following APSCT and effector cell infusions when compared to baseline. |
Pre-transplant and following the third and fourth cellular infusions
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Determine the Methods of Tumor Cell Killing of the in Vivo CD8+ Cells: Cytotoxicity Assays, Blocking Experiments, Analysis of T-cell Receptor (TCR)
大体时间:Pre-transplant and following the third and fourth cellular infusions.
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We will isolate the CD8+ populations (CD3+CD8+, CD8+CD56+) using the Auto MACS (Miltenyi) and then identify the mechanisms of tumor cell killing by the CD8+ cells obtained pre-transplant (Baseline) and following the third and fourth cellular infusions.
We will examine mechanisms of tumor cell killing through NKG2D receptor, major histocompatibility complex (MHC) Class I molecules or through the T cell receptor.
We postulate the CD8+ cells obtained from patient's blood will kill tumor cells both via MHC Class I and through the NKG2D receptor.
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Pre-transplant and following the third and fourth cellular infusions.
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合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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