Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30)

Обзор

This Phase I study will evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes modified to express a constitutively active IL7 receptor (C7R) and a chimeric antigen receptor (CAR) for CD30 (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas. Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of the investigational product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by infusion of autologous C7R.CD30-CAR-EBVSTs. The primary objective is to evaluate safety. Secondary and exploratory objectives include evaluation of antitumor effect, expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.

Подробное описание

This is a Phase I study to evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes (EBVSTs) genetically modified to express a constitutively active interleukin-7 receptor (C7R) and a CD30-specific chimeric antigen receptor (CAR) (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas. The study will also evaluate the antitumor effect of C7R.CD30-CAR-EBVSTs, the expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.

Autologous CD30 CAR T cells have demonstrated clinical activity in patients with relapsed or refractory CD30-positive lymphomas but have shown limited persistence. Epstein-Barr virus-specific T lymphocytes (EBVSTs) have demonstrated long-term persistence following adoptive transfer. In this study, EBVSTs are used as the cellular platform to express both a CD30 CAR and a constitutively active IL7 receptor (C7R). The investigational cell product also provides a mechanism for rapid elimination of transduced cells if clinically indicated.

Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of an autologous C7R.CD30-CAR-EBVST product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of C7R.CD30-CAR-EBVSTs. Participants who meet retreatment criteria, as defined in the protocol, may receive additional treatment cycles. Following treatment, participants will undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status.

Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy.

Participants are followed longitudinally for up to 15 years after the most recent infusion.

Вмешательства

• Биопрепарат Autologous C7R.CD30-CAR-EBVSTs
  Autologous Epstein-Barr virus-specific T lymphocytes genetically modified to express a constitutively active interleukin-7 receptor (C7R), a CD30-specific chimeric antigen receptor (CAR), and an inducible caspase 9 (iC9) safety switch. The investigational product is manufactured from autologous peripheral blood mononuclear cells and administered by intravenous infusion following lymphodepleting chemotherapy.

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.]

Вторичные конечные точки (1)

• Antitumor Effect [Срок оценки: 4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.]

Критерии участия

Procurement Inclusion Criteria:

Participants must meet the protocol-defined procurement eligibility criteria before collection of peripheral blood mononuclear cells for manufacture of the investigational product, including:

• Diagnosis of relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma.
• CD30 positive tumor (can be pending at this time) as assayed in a CLIA certified Pathology Laboratory.
• Age 16 to 75 years.
• Hemoglobin ≥7.0(may be transfused value).
• Karnofsky or Lansky score of > 60%
• Informed consent explained to, understood by and signed by patient or guardian. Patient or guardian given copy of informed consent.

Procurement Exclusion Criteria:

• Active HIV or HTLV infection (testing may be pending at procurement).
• Active bacterial, fungal, or viral infection.

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Treatment Inclusion Criteria:

Participants with a successfully manufactured product must continue to satisfy the protocol-defined treatment eligibility criteria before receiving study treatment, including:

• Diagnosis and clinical course falling into one of the following categories:

• Hodgkin lymphoma
• CD30+ aggressive B-cell lymphoma
• ALK-negative anaplastic T cell lymphoma or other peripheral T- cell lymphoma
• ALK-positive anaplastic T cell lymphoma
• CD30 expression confirmed in a CLIA-certified laboratory. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy
• Age 16 to 75 years.
• Bilirubin ≤ 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be Bilirubin ≤ 3 times the upper limit of normal).
• AST ˂ 3 times the upper limit of normal
• Estimated GFR > 50 mL/min
• Pulse oximetry of > 90% on room air
• Karnofsky or Lansky score of > 60%
• Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after study is concluded. Male partner should use a condom
• Informed consent explained to, understood by and signed by patient/guardian. Patient/Guardian given copy of informed consent.

Treatment Exclusion Criteria:

• Received an investigational cell therapy or vaccine within the past 6 weeks.
• Received an investigational small molecule within the past 2 weeks.
• Received anti-CD30 antibody-based therapy within the previous 4 weeks.
• History of hypersensitivity reactions to murine protein-containing products
• Pregnancy or breastfeeding.
• Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion)
• Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
• Active significant, uncontrolled bacterial, viral or fungal infection.
• Symptomatic cardiac disease (NYHA Class III or IV disease).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Houston Methodist Hospital — Houston

Идентификаторы

NCT: NCT07729397 · ANCILE-30

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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