재발성/불응성 B세포 비호지킨 림프종(NHL)이 있는 성인의 T세포 치료(EB103) (STARLIGHT-1)
재발성/불응성(R/R) B세포 비호지킨 림프종(NHL) 성인을 대상으로 한 EB103 T세포 치료에 대한 공개 라벨, 용량 증량, 다기관 I/2상 임상 시험
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Teresa Klask, MBA
- 전화번호: 925-949-9314
- 이메일: teresa.klask@eurekainc.com
연구 연락처 백업
- 이름: Pei Wang, PhD
- 전화번호: 510-654-7045
- 이메일: pei.wang@eurekainc.com
연구 장소
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California
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Sacramento, California, 미국, 95817
- 모병
- University of California, Davis
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부수사관:
- Mehrdad Abedi, MD
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수석 연구원:
- Naseem Esteghamat, MD MS
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연락하다:
- Sylwia Blawat, DPT, MS
- 전화번호: 916-402-7182
- 이메일: sdblawat@health.ucdavis.edu
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연락하다:
- Dara Feleciano, RN, MSN
- 전화번호: 916-475-9904
- 이메일: djfeleciano@health.ucdavis.edu
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Ohio
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Cleveland, Ohio, 미국, 44106
- 모병
- University Hospitals Seidman Cancer Center
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연락하다:
- Magdalen Sheets, RN, BSN, OCN
- 전화번호: 216-286-6488
- 이메일: Magdalen.Sheets@UHhospitals.org
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수석 연구원:
- Ariel Sindel, DO
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Oregon
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Portland, Oregon, 미국, 97239
- 모병
- Oregon Health and Sciences University
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연락하다:
- 전화번호: 503-494-1080
- 이메일: trials@ohsu.edu
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연락하다:
- Knight Cancer Institute
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수석 연구원:
- Andy Chen, MD, PhD
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Texas
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Dallas, Texas, 미국, 75246
- 모병
- Baylor Scott & White Research Institute, Texas Oncology
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연락하다:
- Philip Millsap
- 전화번호: 214-820-7381
- 이메일: corchemebmt@BSWHealth.org
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수석 연구원:
- Luis Pineiro, MD
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Utah
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Salt Lake City, Utah, 미국, 84143
- 모병
- Intermountain Health, Canyons Region, LDS Hospital
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연락하다:
- Joshua Kunz
- 전화번호: 801-408-4712
- 이메일: Joshua.kunz@imail.org
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수석 연구원:
- Brad Hunter, MD, MP
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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Age 18 years or older at the time of informed consent
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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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: 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. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
To assess the safety and tolerability of EB103.
기간: 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
|
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To determine the Recommended Phase II Dose (RP2D) of EB103 (in Phase 1, Dose Escalation)
기간: Time Frame: 16 months
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RP2D based on maximum tolerated dose (MTD) (if reached), overall safety, preliminary efficacy, and manufacturing capability. |
Time Frame: 16 months
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
To assess the Overall Response Rate of EB103 in our study subject population.
기간: Time Frame: Up to 2 years
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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
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To assess the Disease Control Rate of EB103 in our study subject population.
기간: Time Frame: Up to 2 years
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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
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To assess the Duration of Response and duration of complete response of EB103 in our study subject population.
기간: Time Frame: Up to 2 years
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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
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To assess the Progression-Free Survival rate of EB103 in our study subject population.
기간: 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
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To assess the Event-Free Survival rate of EB103 in our study subject population.
기간: Time Frame: Up to 2 years
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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
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To assess the Overall Survival rate of EB103 in our study subject population.
기간: 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
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To characterize the pharmacokinetic (PK) profile of EB103 by measuring the peak exposure (Cmax).
기간: Time Frame: Up to 2 years
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The peak exposure (Cmax) will be measured in our study subject population. |
Time Frame: Up to 2 years
|
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To characterize the pharmacokinetic (PK) profile of EB103 by measuring the time to reach peak exposure (Tmax).
기간: 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).
기간: 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
|
공동 작업자 및 조사자
협력자
협력자
수사관
수사관
- 연구 책임자: Pei Wang, PhD, Eureka Therapeutics Inc.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- EBUS22CD19AR100
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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