NCT04131738已完成1 期
A Single-Arm, Open-Label Phase I Clinical Trial of a JAK Inhibitor, Baricitinib, for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Cumulative incidence of graft failure
研究概览
简要总结
In this trial, the investigators will begin to explore the possibility that, as in mice, JAK1/2 inhibition with hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) while retaining engraftment and Graft-versus-Leukemia (GVL). Both preclinical and clinical data suggest that inhibition of IFNy and IL-6, directly and using downstream JAK Inhibitors, may be an effective strategy to decrease toxicities and improve disease control for patients undergoing Allogeneic HSCT. Baricitinib, as a JAK1/2 inhibitor, has shown superiority to other JAK inhibitors in preclinical GVHD models. The purpose of this phase I clinical trial is to determine the safety of baricitinib with HSCT measured by the effect on engraftment and grade III-IV acute graft-versus-host-disease (aGVHD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.
- •Diagnosis of a hematological malignancy listed below:
- •Acute myelogenous leukemia (AML) in complete morphological remission (based on IWG Criteria).
- •Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria).
- •Myelodysplastic syndrome with less than 10% blasts in bone marrow.
- •Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete or partial remission.
- •Planned treatment is myeloablative or reduced intensity conditioning followed by peripheral blood HLA matched donor transplantation
- •Available HLA-identical donor who meets the following criteria:
- •At least 18 years of age.
- •HLA-identical donor/recipient match by high-resolution typing per institutional standards.
- •In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC.
- •No active hepatitis.
- •Negative for HTLV and HIV.
- •Not pregnant.
- •Donor selection will be in compliance with institutional standards
- •Safety Lead-In Phase: For the first three patients at each dose level, related donors must consent to a second product collection should it prove necessary.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Adequate organ function as defined below:
- •Total bilirubin must be within normal range at baseline.
- •AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.
- •Estimated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault Formula.
- •Oxygen saturation ≥ 90% on room air.
- •LVEF ≥ 40%.
- •FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation.
- •At least 18 years of age at the time of study registration
- •Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
- •Must be able to receive GVHD prophylaxis with tacrolimus, mini-methotrexate with or without ATG or post transplant Cy with MMF and tacrolimus as outlined in the protocol
排除标准
- •Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary.
- •Known HIV or active hepatitis B or C infection.
- •Known latent tuberculosis infection, or at high risk for latent TB infection, or a positive t-spot tuberculosis test
- •Known hypersensitivity to one or more of the study agents, including baricitinib.
- •Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 35 days after transplant.
- •Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -3).
- •Pregnant and/or breastfeeding.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded.
- •History of unprovoked thrombosis or known thrombophilia. Provoked and/or superficial DVTs are eligible provided they are treated and resolved at the time of screening.
- •Recent (less than 1 year from screening) myocardial infarction or embolic stroke
研究组 & 干预措施
Baricitinib 2 mg Dose Level
Experimental
- On Day 0 the allograft will be infused per standard institutional practice
- Baricitinib will be administered PO at a starting dose of 2 mg daily from Day -3 to Day 100
- After Day 100, for patients already dose reduced to 2 mg daily, reduce baricitinib to 2 mg every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue.
干预措施: Baricitinib (Drug)
Baricitinib 4 mg Dose Level
Experimental
- On Day 0 the allograft will be infused per standard institutional practice
- Baricitinib will be administered PO at a starting dose of 4 mg daily from Day -3 to Day 100
- After Day 100, for patients at a dose of 4 mg daily, reduce baricitinib to 2 mg daily for one month, then every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue.
干预措施: Baricitinib (Drug)
结局指标
主要结局
Cumulative incidence of graft failure
时间窗: 28 days post transplant
-Failure to engraft will be defined as failure to achieve absolute neutrophil count \> 500 for 3 days by Day 28.
Cumulative incidence of grade III-IV acute GVHD
时间窗: Day 100
-Acute GVHD will be assessed using MAGIC criteria
次要结局
- Treatment related mortality(Day 180)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell TransplantationAcute Myelogenous LeukemiaAcute Lymphocytic LeukemiaMyelodysplastic SyndromesNon-Hodgkin LymphomaHodgkin DiseaseNCT03755414Washington University School of Medicine55
招募中
1 期
Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage LeukemiaALL, Childhood B-CellAcute Lymphoid Leukemia RelapseAcute Lymphocytic Leukemia RefractoryNCT05366218University Hospital Tuebingen20
招募中
2 期
JS-201 Combined With Lenvatinib in the Treatment of Small-cell Lung CancerSmall-cell Lung CancerNCT04951947Hunan Province Tumor Hospital30
已完成
1 期
Study to Assess dHER2+AS15 Cancer Vaccine Given in Combination With Lapatinib to Patients With Metastatic Breast CancerMetastatic Breast CancerNCT00952692Michael Morse, MD12
已完成
1 期
Study Testing the Biologic Activity and Safety of an Immunotherapeutic in Patients With Newly Diagnosed Stage IV Kidney CancerRenal Cell CarcinomaNCT00272649Argos Therapeutics22