A Pilot Trial of a WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation
试验速览
- 阶段
- 不适用
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations)
研究概览
简要总结
The purpose of this study is to see if the investigator can help the immune system to work against myeloma through the use/administration of a peptide vaccine (immunotherapy agent) directed against the Wilms Tumor 1 (WT1) protein called galinpepimut-S (or GPS, for brief). Because cancer is produced by the patient's own body, the immune system does not easily recognize and fight cancer cells. The immune system needs to be "trained" to do this; the latter goal is accomplished by using a vaccine consisting of selected fragments of the target antigen, in this case, WT1.
This disease has been selected for this study because the WT1 protein is often present in myeloma cells. WT1 is a gene that is involved in the normal development of kidneys and other organs. When the WT1 gene becomes abnormal, it can make proteins involved in the development of cancer, i.e., can acquire the properties of a true "oncogene". This study will determine whether the vaccine against the WT1 antigen (present in malignant plasmacytes) can cause an immune response which is safe, but also able to keep the myeloma from either coming back or progressing.
详细描述
Key Features:
- This is a Phase 1/2 clinical study conducted in patients with newly diagnosed high-risk multiple myeloma to examine the effects of GPS immunotherapy on clinical and immunobiological indices. The study is titled "A Pilot Trial of a WT1 Analog Peptide Vaccine (Galinpepimut-S) in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation" and is designed as a single-arm, single-institution, open-label study.
Rationale:
- Overexpression of WT1 in multiple myeloma (MM) cells has been demonstrated by immunocytochemistry (IHC) and in HLA-A*0201 patients by staining with a high-affinity fully human IgG1 mAb (ESK1) specific to the RMFPNAPYL/HLA-A*0201 complex on malignant plasma cells. WT1 also serves as a target for antigen-specific directly immunizing immunotherapeutic approaches, such as peptide vaccines (in this case, galinpepimut-S), in patients with multiple myeloma. Patients with persistent plasma cell leukemia following CD34+-selected allografts treated with adoptive transfer of donor-derived WT1-specific cytotoxic T cells are capable of achieving long-lasting complete remission (CR) status, thus underscoring the therapeutic potential of activated T-cells specifically immunized against WT1 peptides. The above provide the theoretical basis for the possibility of successful immunization after exposure to a WT1-specific vaccine (such as galinpepimut-S), whereby WT1-sensitized T-lymphocytes (both CD8+ and CD4+) from vaccinated MM could be directed to antigen (WT1) expressed on malignant plasma cells.
Galinpepimut-S (GPS) - Key features:
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
- •Symptomatic multiple myeloma, ISS stage 1-3 with confirmed diagnosis of multiple myeloma at MSKCC
- •Patients must be eligible to undergo autologous stem cell transplantation by standard institutional criteria
- •Patients must have documented WT1 positive disease. For purpose of this study, this is defined as detectable presence of WT1 expression by immunohistochemistry or by WT1 transcript via RT-PCR on a bone marrow or other plasma cell-related biopsy specimen prior to autologous stem cell transplantation. Bone marrow or other biopsy specimen from time of diagnosis from patients diagnosed at MSKCC or outside hospital may be requested for assessment of WT1 expression by IHC
- •Age > or = to 18 years
- •Karnofsky performance status > or = to 50%
- •Hematologic parameters:
- •Absolute neutrophil count (ANC) > or = to 1,000/μl
- •Platelets > 50,000/μl
- •Biochemical parameters:
- •Total bilirubin < than or = to 2.0 mg/dl
- •AST and ALT < than or = to 2.5 x upper limits of normal (ULN)
- •Creatinine < than or = to 2.0 mg/dl
排除标准
- •Pregnant or lactating women
- •Patients with active infection requiring systemic antimicrobials
- •Patients taking systemic corticosteroids
- •Patients with serious unstable medical illness
- •Concurrent malignancies
研究组 & 干预措施
Galinpepimut-S + Montanide + GM-CSF
Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
干预措施: Galinpepimut-S (Biological)
Galinpepimut-S + Montanide + GM-CSF
Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
干预措施: GM-CSF (Biological)
Galinpepimut-S + Montanide + GM-CSF
Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
干预措施: Montanide (Other)
Galinpepimut-S + Montanide + GM-CSF
Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
干预措施: lenalidomide (Drug)
Galinpepimut-S + Montanide + GM-CSF
Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
干预措施: bortezomib (Drug)
结局指标
主要结局
WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations)
时间窗: 12 weeks after the initial GPS vaccine (end of first series [GPS x 6 administrations])
Number and percentage of participants with CD4 and/or CD8 immune responses against WT1m measured 12-14 weeks after first GPS administration (6 x administrations)
次要结局
- Progression-free Survival (PFS) From Autologous Stem Cell Transplant (ASCT)(3 years and 8 months)
- Overall Survival (OS) From Autologous Stem Cell Transplant (ASCT)(3 years and 8 months)