NCT05794958招募中1 期
A Phase Ib, Open Label Study to Evaluate Safety of Axicabtagene Ciloleucel Reinfusion (Axi-Cel-2) in Patients With Relapsed and/or Refractory Second Line High-Risk Non-Hodgkin Lymphoma After Standard of Care Axi-Cel
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL.
研究概览
简要总结
This is a phase Ib study to establish safety of Axi-Cel-2 in patients with Large B Cell Lymphoma (LBCL) who are at high risk of relapse.
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
- •Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008:
- •Diffuse large B cell lymphoma (DLBCL); OR
- •primary mediastinal (thymic) large B cell lymphoma; OR
- •transformation of follicular lymphoma (TFL), marginal zone lymphoma to DLBCL; OR
- •high grade B-cell Lymphoma NOS will also be included
- •Patients must be considered high-risk lymphoma (defined as LDH greater than upper limit of normal per institutional cut-off) at or within two weeks of leukapheresis.
- •Subjects must have received at least and a maximum one prior line of therapy for LBCL indication (i.e subjects receiving second line standard of care Axi-Cel will be enrolled in this study).
- •At least 1 measurable lesion on PET-CT or CT scan. If the only measurable disease is lymph-node disease, at least 1 lymph node should be ≥ 1.5 cm.
- •Age 18 years or older
- •Eastern cooperative oncology group (ECOG) performance status of 0 or
- •ECOG 2 permitted if performance status is solely attributed to lymphoma.
- •Normal Organ and Marrow Function
- •ANC ≥ 1,000/uL
- •Platelet count ≥ 75,000/uL
- •Adequate renal, hepatic, pulmonary and cardiac function defined as:
- •Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
- •Serum ALT or AST ≤ 2.5 x ULN (except in subjects with liver involvement by lymphoma)
- •Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
- •Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an Echocardiogram.
- •No clinically significant pleural effusion or ascites
- •Baseline oxygen saturation > 92% on room air
- •Ability to understand and the willingness to sign the written IRB-approved informed consent document. Subjects unable to give informed consent will not be eligible for this study.
- •Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
- •Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for twelve (12) months after receiving the preparative lymphodepletion regimen.
- •If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry or immunohistochemistry per the institutional criteria)
- •Prior therapy washout of at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis
排除标准
- •Prior treatment with CAR-T or adoptive cell therapy.
- •Prior allogeneic transplant.
- •No bridging therapy permitted except for steroids or radiotherapy (bridging therapy with steroids e.g. dexamethasone 40 mg for 5 days or radiotherapy is permitted). Measurable non-irradiated lesion post-apheresis needed for enrollment.
- •Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement.
- •Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel infusion.
- •History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
- •Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.
- •Women who are pregnant or breastfeeding
- •History of invasive malignancy unless the patient has been disease-free for five years.
- •Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, and breast) is eligible.
- •Hormonal therapy in subjects in remission >1 year will be allowed.
- •History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication.
- •In the investigator's judgment, the subject is unlikely to complete all study specific visits or procedures, including follow-up visits, or comply with the study requirements for participation.
研究组 & 干预措施
Safety Run-in phase
Active Comparator
First three patients (maximum of 6) will receive 0.5 x 106/kg CART cells (25% standard dose) as reinfusion product between days 7 through 14 if CRS/ICANS has resolved to a grade 1 or less.
干预措施: Axicabtagene Ciloleucel (Drug)
Phase 1b
Experimental
Up to 20 evaluable subjects will receive the target dose of AxiCel infusion to evaluate efficacy of Axi-Cel-2 in adults with high risk relapsed/refractory LBCL
干预措施: Axicabtagene Ciloleucel (Drug)
结局指标
主要结局
Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL.
时间窗: 28 days
Subjects will be assessment for dose limiting toxicity (DLT) for 28 days after the infusion of Axi-Cel-2
次要结局
- Progression free survival (PFS)(12 months)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Safety and Tolerability Open Label Dose Escalation Study of Acadesine in B-CLL PatientsLeukemia, B-Cell, ChronicNCT00559624Advancell - Advanced In Vitro Cell Technologies, S.A.40
终止
1 期
A Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid LeukemiaAcute Myeloid LeukemiaNCT03922477Hoffmann-La Roche13
进行中（未招募）
2 期
A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin LymphomaNon-Hodgkin LymphomaNCT05283720Genmab264
已完成
1 期
A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)B-Cell MalignanciesNCT02018861Incyte Corporation88
已完成
2 期
Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients with Relapsed/refractory CLLChronic Lymphoid LeukemiaNCT03787264German CLL Study Group46