カルレティキュリン (CALR) 変異骨髄増殖性腫瘍の治療のための JNJ-88549968 の研究
CALR変異骨髄増殖性腫瘍に対するT細胞リダイレクト二重特異性抗体JNJ-88549968の安全性、薬物動態、および薬力学に関する初のヒト研究
The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.
調査の概要
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：Study Contact
- 電話番号：844-434-4210
- メール：Participate-In-This-Study1@its.jnj.com
研究場所
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Arizona
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Goodyear、Arizona、アメリカ、85338
- 募集
- City of Hope Phoenix
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California
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Duarte、California、アメリカ、91010
- 募集
- City of Hope
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Colorado
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Aurora、Colorado、アメリカ、80045
- 募集
- UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
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Florida
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Tampa、Florida、アメリカ、33612
- 募集
- Moffit Cancer center
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Georgia
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Atlanta、Georgia、アメリカ、30322
- 募集
- Emory University
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Illinois
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Zion、Illinois、アメリカ、60099
- 募集
- City of Hope Chicago
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- 募集
- University of Michigan
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Grand Rapids、Michigan、アメリカ、49546
- 募集
- Start Midwest
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New Jersey
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East Brunswick、New Jersey、アメリカ、08816
- 募集
- START New Jersey
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New Brunswick、New Jersey、アメリカ、08901
- 募集
- Rutgers Cancer Institute of New Jersey
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New York
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New York、New York、アメリカ、10065
- 募集
- Memorial Sloan Kettering Cancer Center
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The Bronx、New York、アメリカ、10467
- 募集
- Montefiore Medical Center
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North Carolina
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Charlotte、North Carolina、アメリカ、28204
- 募集
- Levine Cancer Institute
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- 募集
- University of Pennsylvania
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South Carolina
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Greenville、South Carolina、アメリカ、29605
- 募集
- Prisma Health
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- 募集
- Sarah Cannon Cancer Institute
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Texas
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Houston、Texas、アメリカ、77030
- 募集
- MD Anderson Cancer Center
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Washington
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Seattle、Washington、アメリカ、98104
- 募集
- Swedish Cancer Institute
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London、イギリス、SE1 9RT
- 募集
- Guy's and St Thomas' Hospital
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London、イギリス、NW1 2PG
- 募集
- University College London Hospitals Nhs Foundation Trust
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Oxford、イギリス、OX3 7LE
- 募集
- Churchill Hospital
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Haifa、イスラエル、3436212
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- Carmel Medical Center
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Jerusalem、イスラエル、9112001
- 募集
- Hadassah University Hospita Ein Kerem
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Ramat Gan、イスラエル、5266202
- 募集
- Sheba Medical Center
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Tel Aviv、イスラエル、64239
- 募集
- Tel Aviv Sourasky Medical Center
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Bologna、イタリア、40138
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- Policlinico Sant'Orsola Malpighi
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Milan、イタリア、21022
- 募集
- Policlinico di Milano
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Alberta
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Calgary、Alberta、カナダ、T2N 4N1
- 募集
- Arthur J E Child Comprehensive Cancer Centre
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Ontario
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Toronto、Ontario、カナダ、M5G 1Z5
- 募集
- Princess Margaret Cancer Centre University Health Network
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Quebec
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Montreal、Quebec、カナダ、H3T 1E2
- 完了
- Jewish General Hospital
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Badalona、スペイン、08916
- 募集
- Hosp. Univ. Germans Trias I Pujol
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Valencia、スペイン、46010
- 募集
- Hosp. Clinico Univ. de Valencia
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Aachen、ドイツ、52074
- 募集
- Universitaetsklinikum der RWTH Aachen
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Berlin、ドイツ、12203
- 募集
- Charite Campus Benjamin Franklin
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Essen、ドイツ、45147
- 募集
- Med. Universitatsklinik Essen
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Hanover、ドイツ、30625
- 募集
- Medizinische Hochschule Hannover
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Heidelberg、ドイツ、69120
- 募集
- Universitaetsklinikum Heidelberg
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Regensburg、ドイツ、93053
- 募集
- Universitaetsklinikum Regensburg
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Paris、フランス、75475
- 募集
- Hopital Saint Louis
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Pierre-Bénite、フランス、69495
- 募集
- CH LYON SUD - Hematology
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Toulouse、フランス、31059
- 募集
- Institut Universitaire du Cancer Toulouse Oncopole
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Beijing、中国、100032
- 募集
- Peking Union Medical College Hospital
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Hangzhou、中国、310002
- 募集
- The First Affiliated Hospital Zhejiang University School of Medicine
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Tianjin、中国、301617
- 募集
- Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
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Bunkyō City、日本、113 8431
- 募集
- Juntendo University Hospital
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Kashiwa、日本、277 8577
- 募集
- National Cancer Center Hospital East
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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:
- Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
- Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
- Participants with ET and MF with risk characteristics as described in the protocol
- Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (<=) 2
- For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Exclusion Criteria:
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Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
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Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (>=) 3 years after treatment ended are allowed to enter the study
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Prior solid organ transplantation
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Either of the following regarding hematopoietic stem cell transplantation:
- Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
- Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
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History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
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：順次割り当て
- 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 |
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実験的：Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)
In dose escalation (Part 1), participants will receive JNJ-88549968. For myelofibrosis (MF) participants only, the study will explore a Phase 1b cohort in which the janus kinase (JAK) inhibitor ruxolitinib or momelotinib is started in combination with JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule (s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. Additional Cohorts may be added to assess different formulation or delivery methods. In dose expansion (Part 2, Part 2b [US only]), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1, Part 1b [US only]). |
JNJ-88549968 will be administered. For US sites: Ruxolitinib will be administered for participants with MF only. For US sites: Momelotinib will be administered for participants with MF only. |
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 |
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Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
時間枠：Approximately up to 35 days after first dose of study treatment
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Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. For US only: A DLT is any adverse event attributed to study treatment that meets the criteria for severity and duration and that occurs during the evaluation periods unless it can be incontrovertibly attributed to disease or other extraneous cause such as an accident. |
Approximately up to 35 days after first dose of study treatment
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
時間枠：Up to 2 years
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An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
時間枠：Up to 2 years
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An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. |
Up to 2 years
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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 |
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
時間枠：Up to 2 years
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Serum samples will be analyzed to determine concentrations of JNJ-88549968. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
時間枠：Up to 2 years
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Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
時間枠：Up to 2 years
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ORR is defined as the percentage of participants who achieve partial response (PR) and complete response (CR) according to modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) criteria and modified European Leukemia Net (ELN) consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
時間枠：Up to 2 years
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CR rate is defined as the percentage of participants who achieve a best response of CR according to disease as defined in modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
時間枠：Up to 2 years
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TTR is defined for participants who achieved PR or CR as the time from the first dose of study treatment to first response of PR or CR according to modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
時間枠：Up to 2 years
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DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression, as defined in modified IWG-MRT criteria and modified ELN consensus report, or death, whichever comes first. |
Up to 2 years
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Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
時間枠：Baseline up to 2 years
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Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure. |
Baseline up to 2 years
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協力者と研究者
捜査官
- スタディディレクター：Janssen Research & Development, LLC Clinical Trial、Janssen Research & Development, LLC
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
その他の研究ID番号
- 88549968MPN1001
- 2023-505584-36-00 (レジストリ識別子：EUCT number)
- 2023 (米国 NIH グラント/契約)
- 88549968MPN1001 (その他の識別子：Janssen Research & Development, LLC)
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?
IPD プランの説明
The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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。
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。