NCT03755414已完成1 期
A Single-Arm, Open-Label, Pilot Study and Expansion Study of JAK Inhibitor Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical 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
- 55
- 试验地点
- 1
- 主要终点
- Number of Participants With Graft Failure (Pilot Study Only)
研究概览
简要总结
In this trial, the investigators will begin to explore the possibility that, as in mice, janus kinase inhibitor 1 (JAK1) inhibition with haploidentical-hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) and cytokine release syndrome (CRS) while retaining Graft-versus-Leukemia (GVL) and improving engraftment. The purpose of this pilot study is to determine the safety of itacitinib with haplo-hematopoietic cell transplantation (HCT) measured by the effect on engraftment and grade III-IV GVHD.
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 International Working Group (IWG) Criteria)
- •Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria)
- •Myelodysplastic syndrome with ≤ 5% 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 T Cell-replete peripheral blood haploidentical donor transplantation
- •Available human leukocyte antigen (HLA)-haploidentical donor who meets the following criteria:
- •Blood-related family member, including (but not limited to) sibling, offspring, cousin, nephew, or parent. Younger donors should be prioritized.
- •At least 18 years of age
- •HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards.
- •In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cells (HSC).
- •No active hepatitis.
- •Negative for human T-cell lymphotrophic virus (HTLV) and human immunodeficiency virus (HIV).
- •Not pregnant.
- •Safety Lead-In Phase: For the first three patients, the donor 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
- •Aspartate aminotransferase (AST)(SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3.0 x institutional upper limit of normal (IULN).
- •Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 45 mL/min/1.73 m^2 by Cockcroft-Gault Formula.
- •Oxygen saturation ≥ 90% on room air.
- •Left ventricular ejection fraction (LVEF) ≥ 40%.
- •Forced expiratory volume (FEV1) and forced vital capacity (FVC) ≥ 40% predicted, diffusing capacity of the lung for carbon monoxide (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 Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable).
- •Must be able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, and cyclophosphamide
排除标准
- •Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary.
- •Presence of donor-specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of ≥2000 as assessed by the single antigen bead assay.
- •Known HIV or active hepatitis B or C infection.
- •Known hypersensitivity to one or more of the study agents, including Ruxolitinib and Itacitinib.
- •Must not have myelofibrosis (unless they are enrolled Amendment #5 or later) or other disease known to prolong neutrophil engraftment to > 35 days after transplant.
- •Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens.
- •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.
- •Additional Inclusion Criteria Under Amendment 5
- •Five subjects with myelofibrosis will be enrolled in the expansion phase.
- •Three patients whose donors fail to collect the target number of CD34+ cells and the treating physician choses to move forward with the haplo-HCT will be enrolled in the expansion phase.
研究组 & 干预措施
Pilot Study: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently
- To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.
干预措施: Stem cell transplantation (Procedure)
Pilot Study: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently
- To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.
干预措施: Itacitinib (Drug)
Pilot Study: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently
- To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.
干预措施: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) (Other)
Pilot Study: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently
- To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.
干预措施: Human Activity Profile (Other)
Expansion Phase: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently
干预措施: Stem cell transplantation (Procedure)
Expansion Phase: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently
干预措施: Itacitinib (Drug)
Expansion Phase: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently
干预措施: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) (Other)
Expansion Phase: Itacitinib
Experimental
- Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy
- Stem cell transplantation on Day 0
- Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently
干预措施: Human Activity Profile (Other)
结局指标
主要结局
Number of Participants With Graft Failure (Pilot Study Only)
时间窗: By day 35
Failure to engraft will be defined as failure to achieve absolute neutrophil count \>500 for 3 days by day 35.
Number of Participants With Grades III-IV Acute GVHD
时间窗: Through day 100
-Incidence of acute grade III-IV GVHD will be assessed using Mount Sinai Acute GvHD International Consortium (MAGIC) criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
次要结局
- Number of Participants Who Experience Cytokine Release Syndrome (CRS)(Through day 28)
- Number of Participants With Treatment Related Mortality(Day 180)
- Cumulative Incidence of Grades II-IV Acute GVHD (Expansion Phase)(Day 100)
研究者
研究点 (1)
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