Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion) (RevSTAR-123)
CD123 표적 모듈(R-TM123)과 병용한 역 키메라 항원 수용체(Allo RevCAR01 T)를 보유하는 유전자 변형 T 세포로 구성된 Allo-RevCAR01-T-CD123의 다기관, 공개 라벨, 1상 연구 CD123에 대해 양성인 선택된 혈액학적 악성종양
The Allo-RevCAR01-T-CD123 drug is a combination of a cellular component (Allo-RevCAR01-T) with a recombinant antibody derivative (R-TM123), which together form the active drug. The cellular component Allo-RevCAR01-T consists of an allogeneic human T-cell genetically multi-edited and expressing a reversed, universal chimeric antigen receptor (RevCAR) presenting an extracellular peptide epitope (RevCAR epitope). R-TM123 functions as a bridging module between Allo-RevCAR01-T and a CD123-expressing target cancer cell by selectively binding the RevCAR epitope and CD123.
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Katja Jersemann, Dr.
- 전화번호: 0493514466450
- 이메일: AVC-201-01@avencell.com
연구 연락처 백업
- 이름: Antje Warth, Dr.
- 전화번호: 0493514466450
- 이메일: AVC-201-01@avencell.com
연구 장소
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Gelderland
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Rotterdam, Gelderland, 네덜란드, 3015
- 모병
- Erasmus University Medical Center
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연락하다:
- Mojca Jongen-Lavrencic, Dr.
- 이메일: m.lavrencic@erasmusmc.nl
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HV
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Amsterdam, HV, 네덜란드, 1081
- 모병
- Amsterdam University Medical Center
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연락하다:
- Arjan van de Loosdrecht, Prof.
- 이메일: a.vandeloosdrecht@amsterdamumc.nl
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RB Groningen
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Groningen, RB Groningen, 네덜란드, 9700
- 완전한
- University Medical Center Groningen (UMCG)
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Cologne, 독일, 50937
- 완전한
- Universitätsklinikum Köln
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Essen, 독일, 45147
- 아직 모집하지 않음
- Universitätsklinikum Essen
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연락하다:
- Bastian von Tresckow, Prof.
- 이메일: bastian.vontresckow@uk-essen.de
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Frankfurt, 독일, 60590
- 아직 모집하지 않음
- Universitätsklinikum Frankfurt
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연락하다:
- Gesine Bug, MD
- 이메일: gesine.bug@unimedizin-ffm.de
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Hamburg, 독일, 20246
- 아직 모집하지 않음
- Universitätsklinikum Hamburg-Eppendorf
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연락하다:
- Franziska Westendorf, MD
- 이메일: f.westendorf@uke.de
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Hanover, 독일
- 모병
- Medizinische Hochschule Hannover
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연락하다:
- Felizitas Thol, Prof.
- 이메일: Thol.Felicitas@mh-hannover.de
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Heidelberg, 독일, 69120
- 아직 모집하지 않음
- Universitätsklinikum Heidelberg
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연락하다:
- Tim Sauer, MD
- 이메일: tim.sauer@med.uni-heidelberg.de
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Baden-Wurttemberg
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Ulm, Baden-Wurttemberg, 독일, 89081
- 모병
- Universitätsklinikum Ulm
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연락하다:
- Elisa Sala, MD
- 이메일: elisa.sala@uniklinik-ulm.de
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Bavaria
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Munich, Bavaria, 독일, 81377
- 모병
- Klinikum der Universität München
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연락하다:
- Marion Subklewe, Prof.
- 이메일: Marion.Subklewe@med.uni-muenchen.de
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Würzburg, Bavaria, 독일, 97080
- 모병
- Universitätsklinikum Würzburg
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연락하다:
- Chatterjee Manik, MD
- 이메일: Chatterjee_m@ukw.de
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Hesse
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Marburg, Hesse, 독일, 35032
- 모병
- Universitätsklinikum Marburg
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연락하다:
- Stephan Metzelder, Prof.
- 이메일: metzelde@med.uni-marburg.de
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Saxony
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Dresden, Saxony, 독일, 01307
- 모병
- Universitätsklinikum Dresden
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연락하다:
- Martin Wermke, Prof.
- 이메일: martin.wermke@ukdd.de
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State of Berlin
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Berlin, State of Berlin, 독일, 13353
- 모병
- Charité Universitätsmedizin Berlin
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연락하다:
- Jörg Westermann, Prof.
- 이메일: joerg.westermann@charite.de
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria (Dose Expansion):
1. Male or female participants, age ≥18 years. 2. HLA type of participant must match at HLA B and C loci 3. Participants with CD123+ AML with morphologically relapsed or refractory disease (>5% BM blasts). CD123 positivity is defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease.
- Up to third relapse for whom all standard or life-extending therapies have failed and for whom no potentially curative therapies are available or who are intolerant to such therapies.
- Without prior myeloproliferative neoplasm (MPN) or MDS/MPN (including leukemic transformation of MPN, "blast phase", and "accelerated phase" MPN), and without hyperproliferative disease requiring cytoreductive treatment within 4 weeks from the screening or with WBC above ULN at screening.
- Exceptions to minimum CD123 expression are not allowed. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Life expectancy of at least 3 months in the judgment of the investigator. 6. Adequate renal and hepatic laboratory assessments. 7. Adequate cardiac function. 8. Long-term central venous access existing (e.g., tunneled CV catheter or port-system) or willing to have such a device inserted to ensure continuous R-TM123 administration.
9. Able to give written informed consent. 10. Weight is greater than the minimum weight required for a specific batch to ensure that the dose administered does not exceed 10^5 TCR+ cells/kg of patient weight.
11. Negative pregnancy; routinely using a highly effective method of birth control.
Exclusion Criteria (Dose Expansion):
- Acute promyelocytic leukemia (t15;17) or myeloproliferative neoplasm (MPN) per WHO 2022 diagnostic criteria.
- AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma).
- Active manifestation of AML in the central nervous system.
- Bone marrow failure syndromes.
- Cardiac disease: heart failure (New York Heart Association III or IV); unstable coronary artery disease, myocardial infarction, or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry.
- Active pulmonary disease with clinically relevant hypoxia (SpO₂ <92% on room air or daily need for supplemental oxygen).
- Parkinson's disease or epilepsy with clinical symptoms in the previous 6 months .
- Stroke, seizure, or intracranial hemorrhage in the past 12 months.
- History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment.
- Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
- Presence of hemorrhagic cystitis
- Other toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
- Allogeneic stem cell transplantation within last 2 months or GvHD requiring systemic immunosuppressive therapy.
- Vaccination with live viruses < 2 weeks prior to lymphodepletion therapy.
- Major surgery within 28 days prior to start of R-TM123 infusion.
- Prior malignancy in the past 3 years or any malignancy requiring ongoing active therapy other than adjuvant endocrine therapy. Participants with malignancy within the last 3 years, but with resected or ablated tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or other tumors considered cured may be considered for the study with Sponsor approval.
- Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives (whichever is shorter) of the substance prior to lymphodepletion.
- Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to lymphodepletion.
- Prior treatment with gene modified cell products.
- Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants.
- Pregnant or breastfeeding women.
- Psychologic disorders with treatment modifications required within the last 3 months, drug and/or significant active alcohol abuse as per investigator's medical judgement. Depression or anxiety due to presence of the underlying malignancy may be exempted with Sponsor approval.
- History of human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
- Known presence of autoantibodies against lupus La protein (La)/ Sjögren syndrome type B antigen (SS-B) or presence or history of autoimmune diseases associated with such antibodies. (Results from recent sampling are not required for eligibility unless MH or other facts indicate La/SS-B would likely be positive.)
- Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids.
- Evidence that the participant is not likely or able to follow the study protocol (e.g., lacking compliance) in the judgment of the investigator.
- Participant unable to understand the informed consent and possible consequences of the participation in the clinical trial in the judgment of the investigator.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Allo-RevCAR01-T-CD123 treatment
Following lymphodepleting therapy (from Day -5 to Day -3), R-TM123 will be administered as continuous infusion from Cycle 1 Day 1 and then will continue for 20 days. Allo-RevCAR01-T will be administered on Day 1. All participants who tolerate Cycle 1 of R-TM123 and Allo-RevCAR01-T without clear disease progression or safety or other contraindications after Cycle 1, will be considered for consolidation cycles of up to 12 consecutive days each of continuous IV infusion of R-TM123 until relapse, unacceptable toxicity, potentially curative treatment option (alloHSCT), consent withdrawal, or maximum one-year overall treatment time (whichever occurs first). |
Intravenous infusion over 3 days (d-5 to d-3) Intravenous infusion over 3 days (d-5 to d-3) Intravenous infusion over 20 days
다른 이름들:
Allo-RevCAR01-T will be administered as IV infusion on Treatment Day 1
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Safety and tolerability
기간: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
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Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria |
At the end of cycle 1 (in total 28 days, given no treatment interruptions)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Response rate to consolidation treatment cycles
기간: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
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At any timepoint until end of study (6 months after the end of last R-TM123 administration)
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Survival rates
기간: At end of study visit (6 months after the end of last R-TM123 administration)
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At end of study visit (6 months after the end of last R-TM123 administration)
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Evidence of biological and clinical activity including best response rate
기간: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
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At any timepoint until end of study (6 months after the end of last R-TM123 administration)
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공동 작업자 및 조사자
협력자
수사관
- 연구 책임자: Manfred Klevesath, MD, AvenCell Therapeutics, Inc.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- AVC-201-01
- 2022-501797-19-00 (기타 식별자: EU CT Number)
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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