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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Axicabtagene Ciloleucel
  Subjects will receive a re-infusion of Axi-Cel (Axi-Cel-2) if signs and symptoms of cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are ≤ grade 1.

Первичные конечные точки

• Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL. [Срок оценки: 28 days]

Вторичные конечные точки (1)

• Progression free survival (PFS) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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 1. 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Stanford University — Palo Alto

Идентификаторы

NCT: NCT05794958 · IRB-68723 · CCT5068 · NCI-2023-05593

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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