A Phase 2, Single-Arm, Open-Label Study Using Itacitinib as Pre-Modulation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Receiving CAR-T-Cell Therapy
概览
- 阶段
- 2 期
- 干预措施
- Itacitinib
- 疾病 / 适应症
- Diffuse Large B Cell Lymphoma
- 发起方
- H. Lee Moffitt Cancer Center and Research Institute
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Progression Free Survival (PFS)
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The purpose of the study is to assess the safety and efficacy of once daily itacitinib oral administration in participants with diffuse large B-cell lymphoma (DLBCL) who will receive CAR-T cell therapy with axicabtagene ciloleucel (axi-cel).
详细描述
This is a phase 2, single-arm, open-label study to assess the safety and efficacy of once daily itacitinib oral administration in patients with diffuse large B-Cell lymphoma (DLBCL) who will receive CAR-T-cell therapy with axicabtagene ciloleucel (Axi-cel) and have been found to have high levels of systemic inflammation. Approximately n=27 adult males and females, 18 years or older, who will receive treatment for diffuse large B-cell lymphoma (DLBCL) at the Moffitt Cancer Center with a ferritin level greater than 400 ng/ml and C-reactive protein (CRP) level greater than 2 mg/dl (20 mg/l) at screening will be enrolled. Study regimen will consist of itacitinib 200 mg PO QD beginning at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day 30 (30 Days Post-CAR-T-cell therapy). The exact number of days between apheresis and CAR T cell infusion may vary based on CAR T cell manufacturing turnaround. A single infusion of axi-cel therapy will be administered on Day 0. Investigators hypothesize that pre-modulation with itacitinib started approximately 4 weeks prior to CAR-T-cell therapy with axi-cel will improve patient outcomes in those patients with diffuse large B-cell lymphoma (DLBCL) who express high levels of systemic inflammation.
研究者
入排标准
入选标准
- •Patients with a histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) who plan to receive treatment at the Moffitt Cancer Center/
- •Adult males or females who are 18 years of age or older at time of signing informed consent.
- •Must have ability to comprehend and the willingness to sign written informed consent for study participation.
- •Eligible to receive CAR-T cell therapy (axicabtagene ciloleucel) for DLBCL and histological variants.
- •Patients must have a serum ferritin level above 400 mg/mL and C-reactive protein level above 2 mg/dL (20 mg/L) at screening.
- •ECOG performance status 0 to
- •The effects of Itacitinib on the developing human fetus are unknown. For this reason and because Janus kinase (JAK)1-selective inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation as outlined in criteria below: (a) Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow up and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants in their understanding confirmed.(b) Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose of Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. (c) Women of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR \>= 12 months of amenorrhea) are eligible.
- •Patients must be ineligible for stem cell transplant at screening on the basis of active lymphoma.
- •Patients must meet laboratory parameters at screening as defined in protocol
排除标准
- •Patients who are currently receiving or who have received any investigational study agent ≤4 weeks prior to screening visit are ineligible.
- •Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
- •Participants with clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from screening, New York Health Association III or IV heart failure, and circulatory collapse requiring vasopressor or inotropic support
- •Participants with arrhythmias that are not stable on a medical management program within 2 weeks of screening are also excluded.
- •Participants with arrhythmias that are not stable on a medical management program within 2 weeks of screening are also excluded.
- •Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal, opportunistic) of any origin.
- •Participants with a known history or prior diagnosis of immunologic or inflammatory/autoimmune disease affecting the CNS, and unrelated to their disease under study or previous treatment.
- •Known positive Human immunodeficiency virus (HIV) status.
- •Participants with evidence of active and/or chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated.
- •Participants with a history of hepatitis C virus (HCV) infection, HCV must have been treated and cured.
研究组 & 干预措施
Pre-Modulation Treatment
Participants will receive itacitinib 200 mg PO QD beginning at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day 30 (30 Days Post-CAR-T-cell therapy)
干预措施: Itacitinib
Pre-Modulation Treatment
Participants will receive itacitinib 200 mg PO QD beginning at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day 30 (30 Days Post-CAR-T-cell therapy)
干预措施: Chimeric antigen receptor (CAR) T-cell therapy
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: at 6 months
Progression Free Survival is defined as the time from start of treatment to the time of disease progression or death. Among patients treated with axi-cel who have a ferritin \>400 ng/ml and CRP\>2 mg/dl at the time of apheresis, the 6 month PFS was 25%. The primary endpoint of this study will be met if pre-modulation with itacitinib followed by axi-cel leads to a 6 month PFS of 45% or higher.
次要结局
- Incidence of Severe Cytokine Release Syndrome (CRS)(Up to 3 months)
- Overall Survival (OS)(up to 27months)
- Overall Response Rate(at 6 months)
- Progression Free Survival (PFS)(up to 27 months)
- Incidence of Severe Immune efflector cell Associated Neurotoxicity Syndrome (ICANS)(Up to 3 months)