A Phase I Study of Matched Unrelated Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Adverse events
研究概览
简要总结
This is a Phase I, multicenter, open-label, non-randomized study of matched unrelated donor BPX-501 T cell infusion in adult subjects with hematological malignancies presenting with recurrent disease minimal residual disease (MRD) post-allogeneic transplant.
详细描述
Un-manipulated donor lymphocyte infusion (DLI) is used after stem cell transplantation to treat and prevent relapse, to prevent infections and to establish full donor chimerism. The addition of mature T cells which exhibit a broad repertoire of T cell immunity against viral antigens, as well as against cancer antigens, might provide a clinical benefit. However, an expected side effect of the presence of mature T cells is the potential occurrence of acute graft-versus-host disease (aGvHD). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve higher clinical response rate with lower GvHD occurrence. Optimization of DLI dose and schedule as well as strategies of donor T-cell manipulation may lead to the consistent ability to separate GvHD from graft-versus-tumor (GvT) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults and children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects aged ≥ 18 yrs and ≤ 65 yrs;
- •Clinical diagnosis of one of the following hematological malignancies:
- •Myelodysplastic Syndromes
- •Lymphomas
- •Multiple Myeloma
- •Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard;
- •Recurrent disease that presents ≥100 days after, or minimal residual disease (MRD) that presents ≥ 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP);
- •Life expectancy >10 weeks;
- •Signed donor and patient/guardian informed consent;
- •A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1;
- •Performance status: Karnofsky score > 50%;
- •Subjects with adequate organ function as measured by:
- •Bone marrow:
- •> 25% donor T-cell chimerism post-transplant
- •Absolute neutrophil count (ANC) >1 x 109/L
- •Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 45%
- •Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) ≥ 50% predicted (corrected for hemoglobin)
- •Hepatic: direct bilirubin ≤ 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5x ULN
- •Renal: creatinine ≤ 2x of ULN for age.
排除标准
- •≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening;
- •Active central nervous system (CNS) involvement with malignant cells (≤ 2 months prior to consenting);
- •Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion;
- •Positive HIV serology or viral RNA;
- •Pregnancy (positive serum β human chorionic gonadotropin [HCG] test) or breast-feeding;
- •Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation;
- •Bovine product allergy.
研究组 & 干预措施
Rivogenlecleucel & Rimiducid
All subjects will receive 3 courses of rivogenlecleucel (BPX-501 T cells) infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0 and DL2 on Days 30 and 60.
Escalating doses of rimiducid (AP1903) (0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after rivogenlecleucel infusion.
干预措施: rivogenlecleucel (Biological)
Rivogenlecleucel & Rimiducid
All subjects will receive 3 courses of rivogenlecleucel (BPX-501 T cells) infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0 and DL2 on Days 30 and 60.
Escalating doses of rimiducid (AP1903) (0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after rivogenlecleucel infusion.
干预措施: Rimiducid (Drug)
结局指标
主要结局
Adverse events
时间窗: 30 days after last dose of study drug (BPX-501 and/or rimiducid)
Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety
次要结局
未报告次要终点