Phase 1 Study to Determine the Effects of Mesenchymal Stem Cells Secreting Interferon Beta in Patients With Advanced Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of Mesenchymal Stem Cells-Interferon-β (MSC-IFNβ)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of human mesenchymal stem cells with interferon beta (MSC-INFb) that can be given to patients with ovarian cancer and to test the safety of the MSC-INFb.
This is an investigational study. MSC-INFb infusions for ovarian cancer is investigational.
Up to 21 patients will take part in this study. All will be enrolled at MD Anderson.
详细描述
MSCs are a type of stem cell that can be removed from bone marrow samples and grown into many different cell types that can be used to treat cancer. The MSCs used in this study were collected from healthy male donors and are stored in a laboratory at MD Anderson. The use of male cells will help us to detect the cells that are infused versus your own female cells.
The MSCs have been genetically changed in a laboratory at MD Anderson to add proteins called interferons. The MSCs will have genetic material introduced to them by a molecule called a plasmid that will help produce interferon beta. Interferons (IFNs) are proteins that may interfere with the growth of tumors. The MSCs will be grown in the laboratory and tested before they are given to you.
MSC-INFb Dose Levels:
If you are found eligible to take part in this study, you will be assigned to a dose level of MSC-INFb based on when you join this study. Up to 4 dose levels of MSC-INFb will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of MSC-INFb is found.
Your dose level may be lowered if you are not tolerating the MSC-INFb infusions. Your study doctor will discuss this with you.
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 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must be 18 to 90 years in age with histologically documented diagnosis of epithelial ovarian cancer including serous papillary, endometrioid, mucinous, clear cell, poorly differentiated or mixed adenocarcinomas.
- •Patient must have recurrent epithelial ovarian cancer and may have received unlimited prior chemotherapeutic regimens for management of recurrent cancer.
- •Patients should have measurable disease as defined by RECIST 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) that is accessible to biopsy.
- •Zubrod performance status of 0-
- •Absolute neutrophil count (ANC) > 1,000/mm3 and a platelet count > and a platelet count > 30,000/mm
- •Creatinine clearance > 50 mL/min (assessed by Cockcroft Gault estimation).
- •Bilirubin < 1.5 x upper limit of normal (unless Gilbert's syndrome), ALT or AST < 3 x upper limit of normal.
- •No evidence of significant cardiac or pulmonary dysfunction.
- •Patient must have a hemoglobin >/= 9 gm/dl (this may be achieved by transfusion if needed) obtained within 14 days before registration. If a patient receives packed red blood cell transfusion to achieve a hemoglobin level of >/= 9 gm/dl, the hemoglobin level needs to be stable (no drop by more than 1 gm/dl from the post-transfusion hemoglobin level) for at least 1 week.
- •Negative pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- •Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months following last treatment.
- •Patient or patient's legal representative able to provide written informed consent.
排除标准
- •Patients receiving anti-cancer therapy within 21 days before MSC treatment.
- •Target lesion previously embolized, perfused, or irradiated without objective evidence of progression before start of therapy to be considered for response assessment.
- •Patients with uncontrolled symptomatic brain metastases. A scan to confirm absence of brain metastasis is not required.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic obstructive pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Symptomatic effusions due to pleural, pericardial, or peritoneal metastasis of epithelial ovarian cancer.
- •No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated Stage I or II cancer from which the patient is currently in complete remission (at least to 5 years), or any other cancer from which the patient has been disease-free for 5 years. Patients may have dual primaries of endometrial and ovarian cancer.
研究组 & 干预措施
Mesenchymal Stem Cells + Interferon Beta (MSC-INFβ)
MSC-INFβ administered on an outpatient basis via intraperitoneal (IP) infusion. Starting dose: 10^5 MSC/kg once a week for 4 treatments. Up to 4 dose levels of MSC-INFβ tested. Symptom questionnaire completed once a week for 4 weeks.
干预措施: MSC-INFβ (Genetic)
Mesenchymal Stem Cells + Interferon Beta (MSC-INFβ)
MSC-INFβ administered on an outpatient basis via intraperitoneal (IP) infusion. Starting dose: 10^5 MSC/kg once a week for 4 treatments. Up to 4 dose levels of MSC-INFβ tested. Symptom questionnaire completed once a week for 4 weeks.
干预措施: Questionnaires (Behavioral)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Mesenchymal Stem Cells-Interferon-β (MSC-IFNβ)
时间窗: 5 weeks
Maximum Tolerated Dose (MTD) is dose with posterior probability of dose limiting toxicities (DLTs) nearest to 30%, provided the lower bound of the 90% credible interval for the posterior probability of DLT does not exceed 30%. Dose limiting toxicities (DLTs) are those adverse events of grade 3 or 4 that occur up to 1 week after the last dose.
Correlation Between the Number of MSC-IFNβ Infused and the Production of Interferon-β and the Number of MSC-IFNβ Detected at the Tumor Sites Via Tumor Biopsy Pre- and Post-Treatment
时间窗: 5 weeks
次要结局
未报告次要终点