ATTAC-II: A Phase II Randomized, Blinded, and Placebo-controlled Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Patients With Newly-Diagnosed Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 3
- 主要终点
- Comparison of Overall Survival (OS) Between the Active Treatment Group (Arms 1 and 2) and the Control Group (Arm 3)
研究概览
简要总结
The purpose of this research study is to determine if an investigational dendritic cell vaccine, called pp65 DC, is effective for the treatment of a specific type of brain tumor called glioblastoma (GBM) when given with stronger doses of routine chemotherapy.
详细描述
Dendritic cells (DC) are involved in activating, or turning-on, your body's immune system. Your immune system helps guard your body from germs, viruses, and other threats. Although dendritic cells are very strong, the number of them in the body is not high enough to cause a powerful immune response; therefore, more DC are made in a laboratory with cells collected from an individual's blood.
In this study, we will make a vaccine that we hope will educate immune cells to target the pp65 antigen, a type of immune marker in GBM, thus resulting in what we call the pp65 DC vaccine. Use of a vaccine that activates your immune system is a type of immunotherapy. It is hoped that by giving the pp65 DC vaccine as a shot under the skin, the immune system will be activated to attack tumor cells in the brain while leaving normal cells alone.
To see if the pp65 DC vaccine is effective for the treatment of GBM, subjects will be assigned to different treatment groups. Two groups of subjects will receive the pp65 DC vaccine and one group will receive a placebo.
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
- Single (Participant)
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
- •To be assessed at study enrollment prior to standard of care chemo-radiation therapy:
- •Age ≥ 18 years.
- •Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma)
- •The tumor must have a supratentorial component.
- •Must have undergone definitive surgical resection of tumor with less than approximately 3cm x 3cm residual enhancing tumor as product of longest perpendicular planes by MRI.
- •Recovery from the effects of surgery, postoperative infection, and other complications.
- •Diagnostic contrast-enhanced MRI or CT scan of the brain preoperatively and postoperatively.
- •Karnofsky Performance Status of ≥
- •Signed informed consent.
- •For females of childbearing potential, negative serum pregnancy test.
- •Women of childbearing potential and male participants must be willing to practice adequate contraception throughout the study and for at least 24 weeks after the last dose of study drug.
- •To be assessed prior to initiation of adjuvant TMZ:
- •Must have completed RT (targeted total dose of 59.4-60.0 Gy over ≤ 7 weeks) and concomitant TMZ (targeted dose of 75mg/m2/d for ≤ 49 days) therapy without significant toxicity that persisted over 4 weeks.
- •History & physical with neurologic examination prior to initiation of adjuvant TMZ.
- •For patients receiving steroids, daily dose must be ≤ 4 mg.
- •CBC with differential with adequate bone marrow function.
- •Adequate renal function.
- •Adequate hepatic function.
- •Abbreviated
排除标准
- •To be verified in order to randomize subject:
- •Prior invasive malignancy unless disease free for ≥ 3 years.
- •Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
- •Recurrent or multifocal malignant gliomas.
- •HIV, Hepatitis B, or Hepatitis C seropositive.
- •Known active infection or immunosuppressive disease.
- •Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region.
- •Prior radiotherapy to the head or neck, resulting in overlap of radiation fields.
- •Severe, active co-morbidity.
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period.
- •Pregnant or lactating women.
- •Prior allergic reaction to temozolomide, GM-CSF or Td.
- •Prior history of brachial neuritis or Guillain-Barré syndrome.
- •Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry.
- •To be assessed prior to initiation of adjuvant TMZ:
- •Did not start radiation therapy and temozolomide within 7 weeks of surgery.
- •Progression of disease as defined by modified RANO criteria.
- •More than 45 days after completion of radiation therapy and temozolomide
研究组 & 干预措施
Arm 1: pp65-shLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: pp65-shLAMP DC with GM-CSF (Biological)
Arm 1: pp65-shLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: Td (Drug)
Arm 2: pp65-flLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: Td (Drug)
Arm 2: pp65-flLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: pp65-flLAMP DC with GM-CSF (Biological)
Arm 3: unpulsed PBMC and Saline
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: unpulsed PBMC and saline (Biological)
Arm 3: unpulsed PBMC and Saline
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
干预措施: Saline (Drug)
结局指标
主要结局
Comparison of Overall Survival (OS) Between the Active Treatment Group (Arms 1 and 2) and the Control Group (Arm 3)
时间窗: From date of first vaccine until the date of death, up to 48 months
Kaplan-Meier survival curves and the log rank test will be used to characterize and compare OS in patients who received pp65-LAMP mRNA DC vaccine (Arms 1 and 2) and in control patients (Arm 3). OS will be defined as the time between first vaccination and death and will be censored at the last follow-up if death has not occurred.
次要结局
- Flow Cytometric Analysis (T Cell)(baseline, post-vaccine #3)
- Cytokine Array Analysis (IFN-g)(baseline, post-vaccine #3)
- Flow Cytometric Analysis (NK Cell)(baseline, post-vaccine #3)
- Flow Cytometric Analysis (CD4.CD25 T Reg)(baseline, post-vaccine #3)
- Comparison of Progression-free Survival Between the Active Treatment Group (Arms 1 and 2 Combined) and the Control Group (Arm 3)(From date of first vaccine until time disease progression or death without prior progression/recurrence, up to 48 months)
- ELISPOT Assay (pp65)(baseline, post-vaccine #3)
- ELISPOT Assay (Actin)(baseline, post-vaccine #3)