A Phase I Study of WT1 Peptides to Induce Anti-Leukemia Immune Responses Following Autologous or Allogeneic Transplantation for AML, CmML, ALL, MDS, and B Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Safety and Feasibility
研究概览
简要总结
The purpose of this study is to determine the safety and effectiveness of administering Wilms tumor gene 1 (WT1) cancer peptides. Cancer peptides are short pieces of protein that are made in a laboratory to be like the peptides that can be found in cancer. These peptides are intended to be given as a "vaccine" to activate the immune cells in a person to attack his/her cancer. These peptides are mixed with an oily substance called Montanide ISA-51 and a white cell growth factor called Granulocyte-macrophage colony-stimulating factor (GM-CSF) which may help make the immune response stronger.
详细描述
Two subgroups with 2 dose cohorts of up to 6 patients each will be enrolled in this exploratory study in order to attempt to obtain immunologic and clinical data on patients with a variety of hematologic malignancies and amongst those in remission and early relapse. The 2 subgroups of patients will be treated with different schemas depending upon whether they are undergoing or have undergone autologous or allogeneic stem cell transplantation.
For the autologous transplant patients: Immune monitoring will require 90ml peripheral blood before the first immunization, 3-5 ml from the leukapheresis product, 40-90ml peripheral blood before the 4th immunization immunizations, after the last immunization (week 6-8), and at the discretion of the immune monitoring lab, every two months if immunizations are continued.
For the allogeneic transplant patients: Immune monitoring will require 90ml peripheral blood before the first immunization, 40-90ml peripheral blood before the 4th immunization immunizations, after the last immunization (week 6-8), and at the discretion of the immune monitoring lab, every two months if immunizations are continued.
Subjects will be monitored with blood pressure, temperature, and pulse, pre-injection, at 15 and 30 minutes after injection, prior to being allowed to leave the clinic. Diphenhydramine 50 mg, solumedrol 100 mg, and epinephrine 1:1000 (1 mL) must be available bedside (or a clinic code cart must be available). If hypotension (SBP <90mmHg for patients with baseline SBP > 110mmHg or > 20 mmHg decrease for those with baseline SBP< 110 mmHg), urticaria or orofacial or laryngeal edema or bronchospasm occurs, an IV line will be placed and the diphenhydramine 50 mg, solumedrol 100 mg, and epinephrine 1:1000 sq are recommended. In this event, patients will be transported emergently to the emergency room if stabilized or the code team will be contacted if patients continue to have progression of symptoms or worsening hypotension. For fever>101.5, acetaminophen 650 mg may be given orally.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •There are two subgroups of patients: Those undergoing autologous stem cell transplantation and those undergoing allogeneic stem cell transplantation.
- •Autologous transplant subgroup:
- •Patients with the following hematologic malignancies (AML, CML, ALL, B cell malignancies, and myelodysplastic syndrome) who will be undergoing autologous stem cell transplantation.
- •Allogeneic transplantation subgroup:
- •Patients with the following hematologic malignancies (AML, CML, ALL, B cell malignancies, and myelodysplastic syndrome) who have undergone allogeneic stem cell transplantation. There is no limitation on whether myeloablative or non-myeloablative chemotherapy is administered. A 3/6 or greater match is required for patients who have had an allogeneic stem cell transplant.
- •Both subgroups:
- •Subject must be one of the following HLA types: HLA A2, A24, DR15 or DRw53 (includes HLA-DR4, -DR7, and DRw9)
- •Karnofsky performance status must be greater than or equal to 70%.
- •Age ≥ 18 years.
- •Ability to understand and provide signed informed consent that fulfills Institutional Review Board guidelines.
- •Patient must agree to use adequate contraception defined as: for women, one of the following (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills, Depo-Provera, or Lupron Depot), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD); for men, one of the following: (1) surgical sterilization, or (2) a condom used with a spermicide.
- •In order to receive their immunizations, subjects should be:
- •For autologous transplants:
- •At least 2 weeks from prior chemotherapy.
- •Injections 1 and 2 must be completed prior to administration of any growth factor mobilization
- •Injections 3, 4, 5, and 6, to resume 2 or more weeks from the time of their stem cell infusion if there has been no Grade 3 or 4 non-hematologic, major organ toxicity within the preceding 1 week. Non-major organ toxicities must have resolved to grade 2 or less.
- •For allogeneic transplants,
- •At least 2 weeks from the time of their stem cell infusion.
- •Without Grade 3 or 4 non-hematologic major organ toxicity within the preceding 1 week; non major organ toxicities must have resolved to grade 2 or less.
- •We will require demonstration of >50% donor myeloid hematopoiesis, based on microsatellite polymorphisms, prior to enrolling the patients with MDS on the study.
- •Adequate laboratory data as follows:
- •Hematologic function: WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (may transfuse or use erythropoietin to achieve this level), platelets ≥ 50,000/microliter ((may transfuse).
- •Renal and hepatic function: serum creatinine < 1.5 mg/dL, bilirubin < 1.5 mg/dL (except a bilirubin of <2.0 will be permitted for patents with Gilbert's syndrome), SGOT/SGPT < 2 x upper limit of normal.
- •Subjects must have a CD4+ count is > 200/mm. There is no specified requirement for CD8+ T cell count.
- •Urine protein/creatinine ratio (UPC) must be less than 1.
排除标准
- •Corticosteroid (greater than 10mg per day of prednisone or an equipotent dose of another corticosteroid) or other immunosuppressive therapy within the prior 1 week.
- •Pregnant women and nursing mothers.
- •Current or prior history of brain metastases.
- •More than 12 months since their stem cell transplant.
- •HIV +, hepatitis BsAg +, Hepatitis C Ab+.
结局指标
主要结局
Safety and Feasibility
时间窗: 2 years
To determine the safety and feasibility of administering WT1 peptides to subjects who have undergone autologous or allogeneic stem cell transplantation for AML, CML, ALL, B cell malignancies and myelodysplastic syndrome.
次要结局
- Immune Response(2 years)
- Efficacy (PFS and OS)(2 years)
研究者
Michael Morse, MD
Professor of Medicine
Duke University