Autologous Transplantation and Stem Cell-Based Gene Therapy With LVsh5/C46 (CAL-1), a Dual Anti-HIV Lentiviral Vector, for the Treatment of HIV-Associated Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Feasibility of infusion of gene-modified cells, defined as engraftment of >= 1% gene-modified cells at the time of hematopoietic recovery from conditioning (absolute neutrophil count >= 500/mcL, platelets >= 100,000/mcL for three consecutive evaluations)
研究概览
简要总结
This clinical trial studies gene-modified, human immunodeficiency virus (HIV)-protected stem cell transplant in treating patients with HIV-associated lymphoma. Stem cells, or cells which help form blood, are collected from the patient and stored. They are treated in the laboratory to help protect the immune system from HIV. Chemotherapy is given before transplant to kill lymphoma cells and to make room for new stem cells to grow. Patients then receive the stem cells that were collected from them before chemotherapy and have been genetically modified to replace the stem cells killed by the chemotherapy.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and feasibility of infusing gene-modified, HIV-protected hematopoietic stem/progenitor cells (HSPC) after high-dose chemotherapy for treatment of acquired immune deficiency syndrome (AIDS)-related lymphoma.
II. To observe the change in gene-modified cell levels before and after antiviral treatment interruption.
SECONDARY OBJECTIVES:
I. To evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).
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 66 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 seropositive
- •Stable, continuous antiretroviral treatment for at least three months before enrollment, defined as a multi-drug regimen (excluding azidothymidine [AZT])
- •HIV plasma viral load < 50 copies/ml
- •Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:
- •Hodgkin's lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy
- •Non-Hodgkin's lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy
- •Chemotherapy responsive disease
- •Karnofsky performance score >= 70%
- •Subjects must agree to use effective contraception from enrollment through completion of the study
- •Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of enrollment
- •Subjects must be on a prophylactic regimen for pneumocystis carinii pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Renal disease: serum creatinine > 2 times upper limit of normal
- •Liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy
- •Serum bilirubin greater than 3 times the upper limit of normal, unless attributed to Gilbert's syndrome
- •Pulmonary disease: forced vital capacity (FVC) < 60% predicted
- •Pulmonary disease: forced expiratory volume in 1 second (FEV1) < 60% predicted
- •Pulmonary disease: diffusion capacity of the lung for carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
- •Cardiac insufficiency: left ventricular ejection fraction (LVEF) < 50% or coronary artery disease requiring treatment
- •Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
- •Hepatitis B surface antigen positive
- •Hepatitis C virus (HCV) antibody positive and detectable HCV quantitative ribonucleic acid (RNA) with clinical evidence of cirrhosis
- •Requiring active treatment for Toxoplasma gondii
- •Planned radiation therapy after transplant
- •Malignancy other than lymphoma, unless (1) in complete remission and more than 5 years from last treatment, or (2) cervical/anal squamous cell carcinoma in situ or (3) superficial basal cell and squamous cell cancers of the skin
- •History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent (Note: Consent may not be obtained by means of a legal guardian)
- •A medical history of noncompliance with HAART or medical therapy
- •Any concurrent or past medical condition that, in the opinion of the Investigator, would exclude the subject from participation or any psychosocial conditions that would hinder study compliance or follow-up, at the discretion of the Investigator
- •Receipt of a vaccine for HIV-1 or any prior gene modified cell product, at any time
- •Known hypersensitivity to any of the products used in the trial-G-CSF (Neupogen), plerixafor, or any planned components of conditioning regimens
- •Pregnant or nursing women
研究组 & 干预措施
Treatment (gene-modified stem cells)
CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.
STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant on day 0.
Note: Patients continue to receive HAART throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.
干预措施: Gene-Modified HIV-Protected Hematopoietic Stem Cells (Biological)
Treatment (gene-modified stem cells)
CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.
STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant on day 0.
Note: Patients continue to receive HAART throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (gene-modified stem cells)
CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.
STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant on day 0.
Note: Patients continue to receive HAART throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.
干预措施: Transplant Conditioning (Other)
结局指标
主要结局
Feasibility of infusion of gene-modified cells, defined as engraftment of >= 1% gene-modified cells at the time of hematopoietic recovery from conditioning (absolute neutrophil count >= 500/mcL, platelets >= 100,000/mcL for three consecutive evaluations)
时间窗: Up to 15 years
Feasibility of collection of >= 2.1 x 10^6 CD34+ cells/kg for backup cryopreservation and collection of an additional >= 2.5 x 10^6 CD34+ cells/kg for genetic modification
时间窗: Up to 15 years
Feasibility of genetic modification, defined as evidence for gene modified CD34+ cells in the infusion product
时间窗: Up to 15 years
Feasibility of stem cell infusion (STI), defined as the ability to achieve engraftment level and maintain CD4 counts and plasma viremia at levels required for STI eligibility
时间窗: Up to 15 years
Incidence of development of confirmed replication competent lentivirus
时间窗: Up to 15 years
Integration sites of vector sequences in peripheral blood mononuclear cells
时间窗: Up to 15 years
Characterized if clinical symptoms suggest clonal expansion of the HSPC or if molecular assays result in clonal expansion in \> 20% of gene-marked cells.
Incidence of >= grade 3 toxicity related to the infusion of gene-modified cells, defined by Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 15 years
Incidence of confirmed insertional mutagenesis
时间窗: Up to 15 years
次要结局
未报告次要终点