Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion) (RevSTAR-123)
疾患患者の治療を目的とした、逆キメラ抗原受容体（Allo RevCAR01 T）とCD123標的モジュール（R-TM123）を組み合わせた遺伝子組み換えT細胞で構成されるAllo-RevCAR01-T-CD123の多施設共同、非盲検、第1相研究CD123 陽性の選択された血液悪性腫瘍
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.
調査の概要
状態
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：Katja Jersemann, Dr.
- 電話番号：0493514466450
- メール：AVC-201-01@avencell.com
研究連絡先のバックアップ
- 名前：Antje Warth, Dr.
- 電話番号：0493514466450
- メール：AVC-201-01@avencell.com
研究場所
-
-
Gelderland
-
Rotterdam、Gelderland、オランダ、3015
- 募集
- Erasmus University Medical Center
-
コンタクト：
- Mojca Jongen-Lavrencic, Dr.
- メール：m.lavrencic@erasmusmc.nl
-
-
HV
-
Amsterdam、HV、オランダ、1081
- 募集
- Amsterdam University Medical Center
-
コンタクト：
- Arjan van de Loosdrecht, Prof.
- メール：a.vandeloosdrecht@amsterdamumc.nl
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-
RB Groningen
-
Groningen、RB Groningen、オランダ、9700
- 完了
- University Medical Center Groningen (UMCG)
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-
-
-
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Cologne、ドイツ、50937
- 完了
- Universitätsklinikum Köln
-
Essen、ドイツ、45147
- まだ募集していません
- Universitätsklinikum Essen
-
コンタクト：
- Bastian von Tresckow, Prof.
- メール：bastian.vontresckow@uk-essen.de
-
Frankfurt、ドイツ、60590
- まだ募集していません
- Universitätsklinikum Frankfurt
-
コンタクト：
- Gesine Bug, MD
- メール：gesine.bug@unimedizin-ffm.de
-
Hamburg、ドイツ、20246
- まだ募集していません
- Universitätsklinikum Hamburg-Eppendorf
-
コンタクト：
- Franziska Westendorf, MD
- メール：f.westendorf@uke.de
-
Hanover、ドイツ
- 募集
- Medizinische Hochschule Hannover
-
コンタクト：
- Felizitas Thol, Prof.
- メール：Thol.Felicitas@mh-hannover.de
-
Heidelberg、ドイツ、69120
- まだ募集していません
- Universitätsklinikum Heidelberg
-
コンタクト：
- Tim Sauer, MD
- メール：tim.sauer@med.uni-heidelberg.de
-
-
Baden-Wurttemberg
-
Ulm、Baden-Wurttemberg、ドイツ、89081
- 募集
- Universitätsklinikum Ulm
-
コンタクト：
- Elisa Sala, MD
- メール：elisa.sala@uniklinik-ulm.de
-
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Bavaria
-
Munich、Bavaria、ドイツ、81377
- 募集
- Klinikum der Universität München
-
コンタクト：
- Marion Subklewe, Prof.
- メール：Marion.Subklewe@med.uni-muenchen.de
-
Würzburg、Bavaria、ドイツ、97080
- 募集
- Universitätsklinikum Würzburg
-
コンタクト：
- Chatterjee Manik, MD
- メール：Chatterjee_m@ukw.de
-
-
Hesse
-
Marburg、Hesse、ドイツ、35032
- 募集
- Universitätsklinikum Marburg
-
コンタクト：
- Stephan Metzelder, Prof.
- メール：metzelde@med.uni-marburg.de
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-
Saxony
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Dresden、Saxony、ドイツ、01307
- 募集
- Universitätsklinikum Dresden
-
コンタクト：
- Martin Wermke, Prof.
- メール：martin.wermke@ukdd.de
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-
State of Berlin
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Berlin、State of Berlin、ドイツ、13353
- 募集
- Charité Universitätsmedizin Berlin
-
コンタクト：
- Jörg Westermann, Prof.
- メール：joerg.westermann@charite.de
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-
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 (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.
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：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
他の名前：
Allo-RevCAR01-T will be administered as IV infusion on Treatment Day 1
他の名前：
|
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 |
|---|---|---|
|
Safety and tolerability
時間枠：At the end of cycle 1 (in total 28 days, given no treatment interruptions)
|
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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Response rate to consolidation treatment cycles
時間枠：At any timepoint until end of study (6 months after the end of last R-TM123 administration)
|
|
At any timepoint until end of study (6 months after the end of last R-TM123 administration)
|
|
Survival rates
時間枠：At end of study visit (6 months after the end of last R-TM123 administration)
|
|
At end of study visit (6 months after the end of last R-TM123 administration)
|
|
Evidence of biological and clinical activity including best response rate
時間枠：At any timepoint until end of study (6 months after the end of last R-TM123 administration)
|
|
At any timepoint until end of study (6 months after the end of last R-TM123 administration)
|
協力者と研究者
スポンサー
協力者
捜査官
- スタディディレクター：Manfred Klevesath, MD、AvenCell 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
追加の関連 MeSH 用語
その他の研究ID番号
- AVC-201-01
- 2022-501797-19-00 (その他の識別子：EU CT Number)
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。