慢性リンパ性白血病（1L CLL）の一次治療で共有結合型ブルトン型チロシンキナーゼ阻害剤（cBTKi）の投与を受け、治療をやめて長期寛解を達成する参加者に対するベネトクラクスの効果を評価する研究 (BRAVE)
1L CLL に対して共有結合 BTKi を投与されている患者にベネトクラクスを追加すると、長期にわたる長期寛解 (UMRD 10^-4 による) が達成され、休薬期間が可能かどうかを評価する第 II 相、非盲検、前向き単群、多施設共同臨床試験
The main purpose of the study is to evaluate if adding venetoclax to participants receiving cBTKi for the 1L CLL can achieve deep durable remissions of undetectable measurable residual disease [uMRD < or 10^-4 in peripheral blood (PB)] by end of combination treatment (EOCT) to allow off-treatment period.
The acronym BRAVE stands for Btki Responders to Achieve deep remission (or off-treatment periods) with VEnetoclax.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Arkansas
-
Springdale、Arkansas、アメリカ、72762
- Highlands Oncology Group
-
-
Colorado
-
Aurora、Colorado、アメリカ、80012-5405
- Rocky Mountain Cancer Centers (Aurora) - USOR
-
-
Florida
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Jacksonville、Florida、アメリカ、32256-6932
- Cancer Specialists of North Florida
-
-
Indiana
-
Fort Wayne、Indiana、アメリカ、46804
- Fort Wayne Medical Oncology and Hematology, Inc
-
-
Iowa
-
Des Moines、Iowa、アメリカ、50314-3030
- Mission Blood and Cancer - MercyOne Cancer Center
-
-
Maryland
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Bethesda、Maryland、アメリカ、20817-1915
- American Oncology Partners of Maryland, PA
-
-
Massachusetts
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Boston、Massachusetts、アメリカ、02215-5418
- Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center
-
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Nebraska
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Grand Island、Nebraska、アメリカ、68803
- Nebraska Cancer Specialists St Francis - Grand Island
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Omaha、Nebraska、アメリカ、68130-2042
- Nebraska Cancer Specialists
-
-
New Jersey
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East Brunswick、New Jersey、アメリカ、08816-4096
- Astera Cancer Care East Brunswick
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New Mexico
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Farmington、New Mexico、アメリカ、87401
- San Juan Oncology Associates, PC
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Ohio
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Cincinnati、Ohio、アメリカ、45236-2725
- Oncology Hematology Care Inc - Cincinnati - USOR
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Columbus、Ohio、アメリカ、43210
- Ohio State University
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Oregon
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Eugene、Oregon、アメリカ、97401-6043
- Willamette Valley Cancer Institute and Research Center
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Medford、Oregon、アメリカ、97504-8332
- Asante Rogue Regional Medical Center
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Tennessee
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Chattanooga、Tennessee、アメリカ、37404
- Tennessee Oncology, PLLC - Chattanooga
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Nashville、Tennessee、アメリカ、37203
- Tennessee Oncology - Midtown
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Texas
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Houston、Texas、アメリカ、77030
- MD Anderson Cancer Center
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Tyler、Texas、アメリカ、75702
- Texas Oncology- Northeast Texas
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Wisconsin
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Milwaukee、Wisconsin、アメリカ、53226
- Medical College of Wisconsin
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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:
- Diagnosed with CLL and currently receiving a stable dose of cBTKi (i.e., ibrutinib, acalabrutinib, or zanubrutinib) for at least 6 months for 1L treatment with a response of at least a PR per iwCLL criteria
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 2
- Adequate renal and liver function
Exclusion Criteria:
- Prior B-cell lymphoma (Bcl-2) inhibitor therapy
- Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening
- Progressive or stable disease on cBTKi
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
- History of cardiomyopathy
- Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
- Clinically significant cardiovascular disease
- Active bleeding or history of bleeding diathesis
- Pregnant women and nursing mothers
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
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：Venetoclax Added to cBTKi (Commercially Prescribed)
Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (< 10^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label. |
Venetoclax tablets will be administered as per the schedule specified in the arm.
他の名前：
Commercially available cBTKi (ibrutinib or acalabrutinib, or zanubrutinib) will be administered in accordance with its prescribing label. |
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 |
|---|---|---|
|
uMRD4 Rate at EOCT
時間枠：Cycle 12 Day 28 (Cycle length= 28 Days)
|
uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10^-4) from PB. |
Cycle 12 Day 28 (Cycle length= 28 Days)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
時間枠：Up to approximately 12 months
|
Complete response (CR)/complete response with incomplete recovery of the bone marrow (CRi) rate is defined as the percentage of participants with a CR or CRi at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
PR Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 12 months
|
PR rate is defined as the percentage of participants with a PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 12 months
|
ORR is defined as the percentage of participants with a CR/CRi or PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
時間枠：Up to approximately 13 months
|
AE and SAEs will be collected as part of this study at baseline and every clinical visit, until 30 days after the final dose of study treatment. |
Up to approximately 13 months
|
|
Number of Participants Who Withdrew Prematurely from the Study
時間枠：Up to approximately 12 months
|
Participants who discontinued treatment before Cycle 12 Day 28 (cycle length= 28 days). |
Up to approximately 12 months
|
|
Overall Survival (OS)
時間枠：Up to approximately 48 months
|
OS is defined as the time from the first study treatment to death from any cause. |
Up to approximately 48 months
|
|
Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 48 months
|
PFS is defined as the time from the first study treatment to the first occurrence of disease progression (PD) or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 48 months
|
EFS is defined as the time from the first study treatment to the first occurrence of PD, anti-leukemic treatment subsequent to the study treatment, or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR/CRi or PR) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines
時間枠：Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR or CRi ) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Time to Next CLL Treatment (TTNT)
時間枠：Up to approximately 12 months
|
TTNT is defined as the time from the first study treatment to the start of anti-leukemic treatment subsequent to the study treatment or death, whichever occurs first. |
Up to approximately 12 months
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Clinical Trials、Hoffmann-La Roche
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
- ML45219
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
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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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