Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30) (ANCILE-30)
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Premal Lulla, MD
- 電話番号：713-441-1450
- メール：lulla@bcm.edu
研究場所
-
-
Texas
-
Houston、Texas、アメリカ、77030
- Houston Methodist Hospital
-
コンタクト：
- Premal Lulla, MD
- 電話番号：713-441-1450
- メール：lulla@bcm.edu
-
-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
____________________________________________________________________________
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).
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Autologous C7R.CD30-CAR-EBVSTs
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of autologous C7R.CD30-CAR-EBVSTs.
Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of autologous C7R.CD30-CAR-EBVSTs.
Participants who meet protocol-defined retreatment criteria may receive additional treatment cycles.
|
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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of Dose-Limiting Toxicities (DLTs)
時間枠：From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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Dose-limiting toxicity (DLT) is defined as any of the following considered possibly, probably, or definitely related to study cellular products: (1) Grade 5 event without disease progression; (2) CRS: Grade 4, or Grade 3 not improving to ≤Grade 2 within 72 hours despite therapy; (3) ICANS: Grade 4, or Grade 3 not improving within 72 hours despite therapy; (4) Grade ≥3 IEC-HS; (5) Grade 4 neutropenia or thrombocytopenia not attributable to underlying disease or lymphodepleting chemotherapy and not improving to ≤Grade 2 within 42 days, or Grade 3 thrombocytopenia with clinically significant major bleeding; (6) Grade ≥3 vital organ toxicity (except transient hepatic or renal abnormalities improving to ≤Grade 2 within 7 days); (7) other Grade 3 toxicities not attributable to underlying disease or lymphodepleting chemotherapy and not resolving to ≤Grade 2 within 72 hours; (8) Grade ≥2 allergic reaction to T-cell infusion.
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From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Antitumor Effect
時間枠：4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
|
Antitumor effect will be assessed by investigator evaluation of objective response (complete response and partial response) using Lugano criteria.[
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4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
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協力者と研究者
捜査官
- 主任研究者：Helen Heslop, MD、The Methodist Hospital Research Institute
- 主任研究者：Premal Lulla, MD、The Methodist Hospital Research Institute
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- ANCILE-30
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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