Phase 2 Multi-center Study of Anti-Programmed-Death-1 [Anti-PD-1] During Lymphopenic State After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplant [HDT/ASCT] for Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- The Number of Patients That Achieve Complete Response
研究概览
简要总结
Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing due to short-term response and long-term toxicities.
- Studies showed these patients have weak immune against MM due to the immune checkpoint mediated by the PD1/PD-L1 interaction between immune cells and MM. Anti-PD-1 antibody (anti-PD1) disrupts this interaction, thus unleashing immune cell function and leading to killing of MM cells.
- Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant.
- Anti-PD1 has been extensively studied in patients with other cancers. It is very safe and effective and has been FDA-approved. Complications are of mild degree and easy to manage successfully in out-patient setting. Severe complications are rare.
Thus, investigators proposed an efficacy study of anti-PD1 treatment after transplant to improve MM treatment outcomes. This was a collaborative study with Medical College of Wisconsin (headquarter of Center for International blood and Marrow Transplant Research). Investigators hypothesized that anti-PD1 treatment would increase the MM response and the MM control duration when added to the standard MM treatment after transplant. Anti-PD1 was given at the dose and interval, which had been studied previously (200 mg intravenous injection every 3 weeks) between 2 weeks until 6 months after transplant. Subjects were monitored closely during and after anti-PD1 therapy until at least 1 year post transplant. Late complications were followed for 3 years.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with MM (Multiple Myeloma) of any stage
- •Has no Progressive Disease (PD) AND has suboptimal response with primary therapy
- •Has measurable disease
- •Has no prior hematopoietic stem cell transplant of any type
- •Has performance status of 0 or 1 (Eastern Cooperative Oncology, ECOG, Performance Scale)
- •Has had a successful peripheral blood stem cell collection with G-CSF (Filgrastim) +/- Plerixafor (Mozobil) only
- •Be willing and able to provide written informed consent
- •Female subjects of child bearing age should have negative urine or serum pregnancy test
- •Female subjects of child bearing age must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity
- •Male subjects must agree to use an adequate method of contraception
- •Subject must be able to swallow capsules
- •Must demonstrate adequate organ function
排除标准
- •Has history of repeat infections, amyloidosis, hyperviscosity, plasma cell leukemia, POEMS syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma, or IgM myeloma
- •Has known CNS (Central Nervous System) involvement or history of resolved CNS involvement
- •Has an active autoimmune disease or history of autoimmune disease that requires systemic treatment with steroids of immunosuppressive agents.
- •Has active, non-infectious pneumonitis
- •Has diagnosis of immunosuppressive disorder or on immunosuppressive therapy within 7 days of transplant admission
- •Is currently participating in or has previously participated in the study of an investigational drug/device within 4 weeks of transplant admission
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4
- •Has had prior monoclonal antibody, chemotherapy, small molecule therapy, or radiation within 2 weeks of transplant admission
- •Has not recovered from adverse events due to previously administered agent
- •Must be free of additional malignancy for at least 5 years
- •Has an active infection requiring systemic therapy
- •Has known psychiatric or substance abuse disorders that would interfere with requirements of the study
- •Is pregnant or breastfeeding or expecting to conceive
- •Has known HIV, Hepatitis B, or Hepatitis C infection
- •Has clinically significant coagulopathy
- •Has known symptomatic heart failure, unstable angina pectoris, or cardiac arrhythmia
- •Has received any type of hematopoietic cell transplant
- •Has received a live vaccine within 30 days of transplant admission
- •Is or has an immediate family member whos is investigational site or sponsor staff directly involved with this study
研究组 & 干预措施
Anti-PD-1 (MK-3475)
Standard Treatment:
High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide.
Study Treatment:
200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses.
干预措施: Autologous Stem Cell Transplant (Procedure)
Anti-PD-1 (MK-3475)
Standard Treatment:
High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide.
Study Treatment:
200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses.
干预措施: Melphalan (Drug)
Anti-PD-1 (MK-3475)
Standard Treatment:
High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide.
Study Treatment:
200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses.
干预措施: Lenalidomide (Drug)
Anti-PD-1 (MK-3475)
Standard Treatment:
High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide.
Study Treatment:
200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses.
干预措施: MK-3475 (Drug)
结局指标
主要结局
The Number of Patients That Achieve Complete Response
时间窗: 180 days post-transplant
The primary efficacy endpoint is complete response rate. The complete response rate was estimated by the observed proportion of complete responders at day 180. Complete response (CR) was defined as negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow and negative bone marrow flow cytometry.
次要结局
- The Estimated Percentage of Patients Alive at 2 Years(2 Years)
- The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years(2 Years)