Phase 1a/1b Study of Itacitinib (INCB039110) for Cytokine Release Syndrome Prevention and Minimization of Immunosuppression Following Nonmyeloablative Related Partially HLA-mismatched Peripheral Blood Stem Cell Transplant (PBSCT) With High-dose Posttransplantation Cyclophosphamide in Older Patients (Age 60 Years)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of participant deaths
研究概览
简要总结
This research is being done to learn whether drug called itacitinib, which is a novel inflammation- and immune-lowering drug (immunosuppressant), can be given before and after non-myeloablative peripheral blood stem cell transplantation (PBSCT; also known as a 'mini' transplant) to help prevent certain complications such as cytokine release syndrome (CRS) for patients with blood cancers, using peripheral blood from a relative. The investigators will also examine if by using itacitinib the investigators can reduce the duration of MMF (other immune suppressive drug administration posttransplant).
详细描述
The NMA PBSC haplo transplant is associated with a higher risk of morbidity and mortality from the cytokine (IL-6 and others)-driven CRS and perhaps higher incidence of acute and chronic GVHD compared to bone marrow (BM) haplo allografting with post-transplant cyclophosphamide (PTCy). Notably, severe CRS (grade 3 and higher) appears to be more common in older patients (≥ 60 years) and is associated with significantly higher non-relapse mortality (NRM) in this patient group. Itacitinib has demonstrated safety, tolerability, ability to inhibit cytokines, including IL-6. Data also suggest that itacitinib can be administered safely in peri- and post-transplant period in the setting of Posttransplant CY immune prophylaxis and haploPBSCT with no evidence of delayed engraftment or delayed count recovery, with significant reduction in CRS compared to historical control, and a low rate of aGVHD, cGVHD, and NRM, and with no increase in relapse risk. Thus, the investigators propose a clinical study in which itacitinib will be used prophylactically in recipients age 60 years and older to prevent development of severe CRS, reduce severe CRS-associated NRM, and the incidence of severe GVHD, thus allowing further reduction in posttransplant immunosuppression therapy after PTCy-based NMA related partially-mismatched PB allografting.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of a suitable related, HLA-haploidentical (partially mismatched) stem cell donor.
- •Eligible diagnoses:
- •Acute leukemias in complete remission with minimal residual disease
- •Myelodysplastic syndrome (MDS) with at least one poor-risk feature
- •Chronic myelomonocytic leukemia with at least one poor-risk feature
- •T-cell PLL in PR or better prior to transplantation.
- •Tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase.
- •Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
- •Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen
- •Age ≥ 60 years.
- •Adequate end-organ function as measured by:
- •Left ventricular ejection fraction ≥ 35% or shortening fraction > 25%
- •Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN
- •FEV1 and FVC ≥ 40% of predicted
- •ECOG performance status ≤ 2 or Karnofsky score ≥ 60
排除标准
- •No active extramedullary leukemia or known active CNS involvement by malignancy.
- •Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning.
- •No previous allogeneic HSCT.
- •Not pregnant or breast-feeding
- •No uncontrolled infection.
- •No known HIV infection.
- •No active replicating HBV or HCV infection detected by PCR that requires treatment or at risk for HBV reactivation (positive HBsAg)
研究组 & 干预措施
Itacitinib
Itacitinib will be given at 200 mg orally daily from day -3 to day 90. Itacitinib will be given in conjunction with one of four different regimens for immunosuppression. These 4 regimens are listed in Table 2, Section 5.2 of the protocol. Itacitinib may continue beyond day +90 if there is GVHD. NOTE: If patient develops GVHD requiring treatment after all immune suppression, including itacitinib, is stopped on day +90, the itacitinib will not be restarted and the patient will be treated per standard of care.
干预措施: Itacitinib (Drug)
结局指标
主要结局
Number of participant deaths
时间窗: 14 days
Number of participant deaths will be used to assess the efficacy of itacitinib in preventing the occurrence of death.
Number of participants with grade 3 or higher CRS
时间窗: 14 days
Number of participants with grade 3 or higher CRS will be used to assess the efficacy of itacitinib in preventing the development of severe (grade 3 or higher) cytokine release syndrome (CRS).
Number of participants with grade 1-2 CRS that requires additional CRS-directed treatment
时间窗: 14 days
Number of participants with grade 1-2 CRS that requires additional CRS-directed treatment will be used to assess the efficacy of itacitinib in preventing the development of grade 1-2 CRS that requires additional CRS-directed treatment.
Number of participants with treatment limiting toxicities by Day 60
时间窗: 60 days
Number of participants with treatment limiting toxicities by Day 60 will be used to identify the safe PTCy-based immunosuppressive regimen that incorporates itacitinib with tacrolimus and a reduced duration of immunosuppression with mycophenolate (MMF).
次要结局
未报告次要终点