再発性/難治性B細胞性非ホジキンリンパ腫（NHL）の成人におけるT細胞療法（EB103） (STARLIGHT-1)
再発性/難治性（R/R）B細胞非ホジキンリンパ腫（NHL）の成人を対象としたEB103 T細胞療法の非盲検、用量漸増、多施設共同第I/II相臨床試験
This is an open-label, multi-center, Phase 1/2 clinical trial evaluating the safety and effectiveness of EB103 in R/R B-cell NHL patients with the highest unmet medical needs, such as Human Immunodeficiency Virus (HIV)-associated lymphoma, primary and secondary central nervous system (CNS) lymphoma, and a wide range of high-grade B-cell lymphomas (HGBLs), as well as R/R large B-cell lymphoma (LBCL) patients ineligible for autologous transplant.
調査の概要
状態
条件
介入・治療
詳細な説明
EB103 is an engineered T-cell therapy built on the ARTEMIS® Cell Receptor Platform.
This study consists of a completed Phase 1 portion and an ongoing Phase 2 expansion portion.
In Phase 1, a traditional 3+3 dose-escalation design was used to evaluate the safety and tolerability of EB103 and to determine the recommended Phase 2 dose (RP2D). Following dose escalation, an RP2D confirmatory cohort was enrolled to further characterize the safety profile of EB103 at the selected dose.
Phase 2 is an expansion cohort in which additional subjects will be enrolled and treated at the RP2D to further evaluate the safety and preliminary efficacy of EB103.
The active assessment period extends for 2 years (24 months) after the EB103 infusion (Day 0). Subjects then enter long-term follow-up (LTFU) for ongoing safety and overall survival assessments through Year 15.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Teresa Klask, MBA
- 電話番号：925-949-9314
- メール：teresa.klask@eurekainc.com
研究連絡先のバックアップ
- 名前：Pei Wang, PhD
- 電話番号：510-654-7045
- メール：pei.wang@eurekainc.com
研究場所
-
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California
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Sacramento、California、アメリカ、95817
- 募集
- University of California, Davis
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副調査官：
- Mehrdad Abedi, MD
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主任研究者：
- Naseem Esteghamat, MD MS
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コンタクト：
- Sylwia Blawat, DPT, MS
- 電話番号：916-402-7182
- メール：sdblawat@health.ucdavis.edu
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コンタクト：
- Dara Feleciano, RN, MSN
- 電話番号：916-475-9904
- メール：djfeleciano@health.ucdavis.edu
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Ohio
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Cleveland、Ohio、アメリカ、44106
- 募集
- University Hospitals Seidman Cancer Center
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コンタクト：
- Magdalen Sheets, RN, BSN, OCN
- 電話番号：216-286-6488
- メール：Magdalen.Sheets@UHhospitals.org
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主任研究者：
- Ariel Sindel, DO
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Oregon
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Portland、Oregon、アメリカ、97239
- 募集
- Oregon Health and Sciences University
-
コンタクト：
- 電話番号：503-494-1080
- メール：trials@ohsu.edu
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コンタクト：
- Knight Cancer Institute
-
主任研究者：
- Andy Chen, MD, PhD
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Texas
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Dallas、Texas、アメリカ、75246
- 募集
- Baylor Scott & White Research Institute, Texas Oncology
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コンタクト：
- Philip Millsap
- 電話番号：214-820-7381
- メール：corchemebmt@BSWHealth.org
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主任研究者：
- Luis Pineiro, MD
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Utah
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Salt Lake City、Utah、アメリカ、84143
- 募集
- Intermountain Health, Canyons Region, LDS Hospital
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コンタクト：
- Joshua Kunz
- 電話番号：801-408-4712
- メール：Joshua.kunz@imail.org
-
主任研究者：
- Brad Hunter, MD, MP
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
-
Age 18 years or older at the time of informed consent
-
Histologically confirmed R/R B-cell non-Hodgkin's lymphoma (NHL)
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Adequate organ function
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Relapsed or refractory disease
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Relapsed or refractory disease, defined as ONE OR MORE of the following modified SCHOLAR-1 criteria (Crump, 2017):
- Progressive disease (PD) as best response to any line of chemoimmunotherapy
- Stable disease (SD) or partial response (PR) as best response to ≥ 4 cycles of first-line chemoimmunotherapy or to ≥ 2 cycles of later-line chemoimmunotherapy
- Relapse ≤ 12 months of first-line chemoimmunotherapy
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Subjects with PCNSL with following status, if deemed appropriate by the Investigator, can be enrolled:
- Intolerance of high-dose methotrexate (HD-MTX) induction therapy
- Subjects ineligible for autologous hematopoietic stem cell transplantation (Auto HSCT) consolidation of HD-MTX-based induction
- Subjects who have relapsed at any time after Auto HSCT
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Diagnosis and disease assessment
- For Non-CNS B-cell NHL Positron emission tomography (PET)-positive disease assessment according to Cheson 2014
- For PCNSL or secondary CNS lymphoma shall have the initial diagnosis confirmed by International PCNSL Collaborative Group (IPCG) criteria according to Abrey 2005; Barajas, 2021; Hoang-Xuan 2023.
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Eastern Cooperative Oncology Group (ECOG) ≤ 2
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Toxicities due to prior therapy must be stable and recovered to Grade 1 or less
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Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of informed consent and prior to starting conditioning chemotherapy.
Exclusion Criteria:
- Prior CD19-targeted cellular therapy
- History of Richter's transformation of chronic lymphocytic leukemia (CLL)
- History of another primary malignancy that has not been in remission for ≥ 2 years.
- History or presence of clinically relevant Central Nervous System (CNS) pathology
- Clinical or radiological evidence of impending brain herniation or significant mass effect
- Those with PCNSL or secondary CNS lymphoma who have previously received whole brain radiotherapy (WBRT)
- Active cardiac lymphoma involvement which is not responding to treatment
- History of myocardial infarction, cardiac angioplasty and stenting, unstable angina, or other clinically significant cardiac disease within 6 months of informed consent
- Active, uncontrolled systemic bacterial, fungal, or viral infection. Patients with HIV, hepatitis B, or hepatitis C are eligible provided their infection is being treated and the viral load is controlled.
- History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
- History of severe, immediate hypersensitivity reaction to any agents used in this study, including the conditioning chemotherapeutic agents
- Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
- Autologous HSCT within 3 months of informed consent
- Prior allogeneic transplant at least 6 months prior to study enrollment are eligible unless experienced graft-versus-host disease (GvHD) that requires ongoing treatment with systemic steroids or other systemic GvHD therapy, such as a calcineurin inhibitor, within 12 weeks of initial screening
- Live vaccine within 3 months prior to planned start of conditioning regimen
- Inability to adhere to all required washout periods for agents and therapies prior to leukapheresis AND prior to starting conditioning chemotherapy
- Female subjects of childbearing potential who are pregnant or breastfeeding; subjects must agree to abstain from breastfeeding during study participation and for ≥ 1 year after lymphodepleting chemotherapy
- In the Investigator's judgement, the subject is unlikely, unable, or unwilling to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
- All genders who are not willing to use acceptable methods of contraception from the time of informed consent through 12 months after EB103 T-cell infusion
- Any medical condition that, in the Investigator's or the Sponsor's opinion, would impose excessive risk to the subject or ability to assess effect of the study drug.
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：EB103
Experimental: Dose Escalation, RP2D Confirmatory, and Expansion (Phase 1/2 Single Arm) Dose Escalation Cohort: Participants receive a single infusion of EB103 at one of two predefined dose levels on Day 0 (completed). RP2D Confirmatory Cohort: Participants receive EB103 at the RP2D on Day 0. Expansion Cohort: Participants receive an initial EB103 T-cell infusion at the RP2D on Day 0 followed by a second EB103 T-cell infusion administered according to the protocol-defined schedule. |
EB103 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the EB103 transgene. |
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 |
|---|---|---|
|
To assess the safety and tolerability of EB103.
時間枠：Up to 2 years (active assessment period); additional long-term follow-up (LTFU) up to 15 years
|
Type, frequency, and severity of adverse events (AEs), including treatment-emergent AEs (TEAEs), treatment-related AEs (TRAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinically significant laboratory abnormalities recorded as AEs, and AEs leading to permanent discontinuation. |
Up to 2 years (active assessment period); additional long-term follow-up (LTFU) up to 15 years
|
|
To determine the Recommended Phase II Dose (RP2D) of EB103 (in Phase 1, Dose Escalation)
時間枠：Time Frame: 16 months
|
RP2D based on maximum tolerated dose (MTD) (if reached), overall safety, preliminary efficacy, and manufacturing capability. |
Time Frame: 16 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
To assess the Overall Response Rate of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Overall Response Rate (ORR), defined as the proportion of subjects with a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR) will be assessed. |
Time Frame: Up to 2 years
|
|
To assess the Disease Control Rate of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Disease Control Rate (DCR), defined as the proportion of subjects with BOR of either Complete Response (CR), Partial Response (PR), or Stable Disease (SD) will be assessed. |
Time Frame: Up to 2 years
|
|
To assess the Duration of Response and duration of complete response of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Duration of Response (DOR), defined as the time from first response to Progressive Disease (PD) or death will be assessed. The duration of complete response (DOCR), defined as the time from CR to PD or death. |
Time Frame: Up to 2 years
|
|
To assess the Progression-Free Survival rate of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Progression-Free Survival (PFS), defined as the time from EB103 infusion to PD or death will be assessed. |
Time Frame: Up to 2 years
|
|
To assess the Event-Free Survival rate of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Event-Free Survival (EFS) will be defined as the time from EB103 T-cell infusion to the earliest of the following events: death from any cause, PD, or starting a new anticancer therapy. |
Time Frame: Up to 2 years
|
|
To assess the Overall Survival rate of EB103 in our study subject population.
時間枠：Time Frame: Up to 2 years
|
The Overall Survival (OS) will be defined as the time from EB103 T-cell infusion to the date of death. |
Time Frame: Up to 2 years
|
|
To characterize the pharmacokinetic (PK) profile of EB103 by measuring the peak exposure (Cmax).
時間枠：Time Frame: Up to 2 years
|
The peak exposure (Cmax) will be measured in our study subject population. |
Time Frame: Up to 2 years
|
|
To characterize the pharmacokinetic (PK) profile of EB103 by measuring the time to reach peak exposure (Tmax).
時間枠：Time Frame: Up to 2 years
|
Time to reach peak exposure (Tmax) will be measured in our study subject population. |
Time Frame: Up to 2 years
|
|
To characterize the pharmacokinetic (PK) profile of EB103 by measuring the partial area under the curve (pAUC).
時間枠：Time Frame: Up to 2 years
|
Partial area under the curve (pAUC) will be measured in our study subject population. |
Time Frame: Up to 2 years
|
協力者と研究者
捜査官
- スタディディレクター：Pei Wang, PhD、Eureka Therapeutics Inc.
研究記録日
主要日程の研究
研究開始 (実際)
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
- EBUS22CD19AR100
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
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