A Prospective, Open-label, Randomized, Multicenter Phase-III Trial to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation (CLLRT2)
The aim of the trial is to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation
調査の概要
状態
条件
詳細な説明
This trial is a phase 2 study and - according to the definitions of the ICH Harmonized Tripartite Guide-line E8 - a therapeutic exploratory type of study, which is designed as a prospective, multicenter, open label trial. The trial aims to investigate the efficacy and safety of a fixed-duration treatment ap-proach in patients aged 80 years or older and/or those exhibiting symptoms of frailty.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
-
Dublin、アイルランド、Dublin 9
- 募集
- Beaumont Hospital
-
コンタクト：
- Patrick Thornton
- 電話番号：+613 8559 5000
- メール：philip.thompson@petermac.org
-
Galway、アイルランド、H91 YR71
- 募集
- University Hospital Galway
-
コンタクト：
- Amjad Hayat
- 電話番号：+35391544281
- メール：amjad.hayat@hse.ie
-
-
-
-
-
Melbourne、オーストラリア、3000
- 募集
- Peter MacCallum Cancer Center
-
コンタクト：
- Philip Thompson, Prof.
- 電話番号：+613 8559 5000
- メール：philip.thompson@petermac.org
-
-
-
-
-
Innsbruck、オーストリア、6020
- まだ募集していません
- Medizinische Universitaet Innsbruck
-
コンタクト：
- Dominik Wolf, Prof.
- 電話番号：+4351250424003
- メール：mui-oversight@i-med.ac.at
-
Vienna、オーストリア、1090
- 募集
- Medizinische Universität Wien
-
コンタクト：
- Alexander Gaiger
- 電話番号：+4314040044765
- メール：alexander.gaiger@meduniwien.ac.at
-
-
-
-
-
Copenhagen、デンマーク、2100
- まだ募集していません
- Rigshospitalet
-
コンタクト：
- Caspar Da Cunha-Bang, MD
- 電話番号：+4535450410
- メール：Caspar.Da.Cunha-Bang@regionh.dk
-
-
-
-
-
Cologne、ドイツ、50937
- 募集
- Uniklinik Köln
-
コンタクト：
- Barbara Eichhorst, Prof.
- 電話番号：+4922147888220
- メール：barbara.eichhorst@uk-koeln.de
-
Dresden、ドイツ、01307
- まだ募集していません
- Technische Universitaet Dresden
-
コンタクト：
- Johannes Schetelig, Prof.
- 電話番号：+493514585604
- メール：Johannes.Schetelig@ukdd.de
-
Frankfurt、ドイツ、60590
- 募集
- Universitätsklinikum Frankfurt
-
コンタクト：
- Sebastian Scheich
- 電話番号：+496963013767
- メール：s.scheich@med.uni-frankfurt.de
-
Heidelberg、ドイツ、69120
- まだ募集していません
- Universitätsklinikum Heidelberg
-
コンタクト：
- Peter Dreger, Prof.
- 電話番号：+496221568030
- メール：Peter.Dreger@med.uni-heidelberg.de
-
Kiel、ドイツ、24105
- まだ募集していません
- Universitätsklinikum Schleswig-Holstein Campus Kiel
-
コンタクト：
- Matthias Ritgen, Dr.
- 電話番号：+4943150022555
- メール：m.ritgen@med2.uni-kiel.de
-
Ulm、ドイツ、89081
- 募集
- Universitätsklinik Ulm
-
コンタクト：
- Christof Schneider, Dr.
- 電話番号：+4973150056012
- メール：christof.schneider@uniklinik-ulm.de
-
-
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:
-
Age ≥80 years OR considered frail defined by a frailty score of >2 on the FRAIL scale via the patient´s assessment
-
Has documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria3
-
CLL/SLL requiring treatment according to the iwCLL 2018 criteria3
-
Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL:
- Absolute neutrophil count ≥ 1.0 × 10^9/L
- Platelet counts ≥ 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow in-volvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10^9/L if there is bone marrow involvement
- Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to mar-row involvement of CLL)
-
Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 times the institutional upper limit of normal (ULN) value unless directly attributable to the patient's CLL or Gilbert's syndrome
-
Adequate renal function defined by a value ≥30 mL/min, determined either by creatinine clearance directly measured with a 24-hour urine collection or via estimated GFR calculated according to the CKD-EPI equation or Cystatin C measurements (e.g. in sarcopenic patients).
-
Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed repeatedly until 6 months after last month of treatment), negative testing for hepa-titis C RNA within 6 weeks prior to registration
-
Life expectancy ≥ 3 months
-
In case of a recent previous (i.e. debulking) treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods be-fore start of the study treatment in the CLL-Frail2 trial:
- chemotherapy ≥ 28 days
- antibody treatment ≥ 14 days
- corticosteroids may be applied until the start of the study therapy; these have to be re-duced to an equivalent of ≤ 20mg prednisolone per day during treatment
-
Signed informed consent and, in the investigator's judgment, able to comply with the study protocol
-
Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
Exclusion Criteria:
-
1. Previous CLL-directed therapies 2. Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leu-kaemia) 3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML) 4. Uncontrolled autoimmune condition 5. Malignancies other than CLL currently requiring systemic therapies (unless the malignant dis-ease is in a stable remission at the discretion of the treating physician) 6. Uncontrolled infection currently requiring systemic treatment 7. Any serious medical condition or abnormality in clinical laboratory tests that, in the investiga-tor's judgment, precludes the patient's safe participation in and completion of the study 8. Requirement of treatment with any moderate or strong CYP3A4 inhibitor or strong CYP3A4 inducer (≤ 14 days or 5 half-lives, whichever is shorter) before the first dose of study drug, or requiring ongoing treatment with a moderate or strong CYP3A inhibitor or a strong CYP3A in-ducer.
9. Requirement of therapy with phenprocoumon or other vitamin K antagonists 10. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
-
Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring for HBV reactivation
-
Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 11. Major surgery within 4 weeks of the first dose of study drug 12. Any uncontrolled or clinically significant cardiovascular disease including the following:
-
New York Heart Association class III or IV congestive heart failure
-
History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricu-lar fibrillation, torsades de pointes) 13. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand dis-ease if not CLL/SLL related, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 14. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery proce-dures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
15. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration 16. Known hypersensitivity to zanubrutinib or sonrotoclax or any of the excipients 17. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 18. Fertile men or women of childbearing potential unless:
-
surgically sterile or ≥ 2 years after the onset of menopause, or
-
willing to use two methods of reliable contraception including one highly effective contra-ceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 7 days after sonrotoclax and 30 days after zanubrutinib respec-tively 19. Vaccination with a live vaccine <28 days prior to registration 20. Legal incapacity 21. Prisoners or subjects who are institutionalized by regulatory or court order 22. Persons who are in dependence to the sponsor or an 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：ランダム化
- 介入モデル：並列代入
- 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 |
|---|---|
|
アクティブコンパレータ：Arm A: R-(mini)-CHOP
Cycle 1-6 Day 1: Cyclophosphamide 750 mg/m2 iv Doxorubicin 50 mg/m2 iv Vincristine 1.4 mg/m2 (max 2 mg) iv Rituximab 375 mg/m2 iv Day 1-5: Prednisolone 100 mg po If R-CHOP-ineligible*, R-mini-CHOP3 is administered: Cycle 1-6 Day 1: Cyclophosphamide 400 mg/m2 iv Doxorubicin 25 mg/m2 iv Vincristine 1 mg iv Rituximab 375 mg/m2 iv or sc Day 1-5: Prednisolone 100 mg po |
750 mg/m2 iv (R-CHOP) or 400 mg/m2 iv (R-mini-CHOP) 50 mg/m2 iv (R-CHOP) or 25 mg/m2 iv (R-mini-CHOP) 1.4 mg/m2 iv (R-CHOP) or 1 mg/m2 iv (R-mini-CHOP) 375 mg/m2 iv (R-CHOP) or 375 mg/m2 iv or sc (R-mini-CHOP) |
|
実験的：Arm B: Epcoritamab-Pirtobrutinib
12 cycles: Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc Cycle 2-4 Day 1-21: Pirtobrutinib 200 mg QD po Day 1, 8, 15: Epcoritamab 48 mg sc Cycle 5+6 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc Cycle 7-12: Day 1-28: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc For patients with CR, PR or SD after 12 cycles (=EO[C]T), maintenance treatment with pirtobrutinib 200 mg QD until unacceptable toxicity, disease progression or allogeneic stem cell transplantation will be offered. |
Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc Cycle 2-28 Epcoritamab 48 mg sc
他の名前：
Pirtobrutinib 200 mg QD po
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 |
|---|---|---|
|
PFS
時間枠：approx. 40 months after first subject in
|
Investigator-assessed progression-free survival (PFS) according to Lugano criteria |
approx. 40 months after first subject in
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
ORR
時間枠：approx. 40 months after first subject in
|
Overall response rate (ORR) at the end of (combination) treatment according to Lugano criteria |
approx. 40 months after first subject in
|
|
CRR
時間枠：approx. 40 months after first subject in
|
Complete response rate (CRR) at the end of (combination) treatment according to Lugano criteria |
approx. 40 months after first subject in
|
|
Best response according to Lugano criteria
時間枠：approx. 40 months after first subject in
|
Best response according to Lugano criteria |
approx. 40 months after first subject in
|
|
Undetectable minimal residual disease (uMRD)
時間枠：approx. 40 months after first subject in
|
Undetectable minimal residual disease (uMRD) rates in peripheral blood at the end of (combination) treatment |
approx. 40 months after first subject in
|
|
DOR
時間枠：approx. 40 months after first subject in
|
Duration of response (DOR) according to Lugano criteria |
approx. 40 months after first subject in
|
|
Overall survival (OS)
時間枠：approx. 40 months after first subject in
|
Overall survival (OS) |
approx. 40 months after first subject in
|
|
TTNT
時間枠：approx. 40 months after first subject in
|
Time to next treatment (TTNT) |
approx. 40 months after first subject in
|
|
TFS
時間枠：approx. 40 months after first subject in
|
Treatment-free survival (TFS) |
approx. 40 months after first subject in
|
|
SCT
時間枠：approx. 40 months after first subject in
|
Proportion of patients receiving allogeneic stem cell transplantation (SCT) for consolidation |
approx. 40 months after first subject in
|
協力者と研究者
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
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 有機化学物質
- 複素環化化合物
- 複素環化化合物、2リング
- 複素環化化合物、融合リング
- 炭化水素
- 炭化水素、周期的
- 炭水化物
- アルカロイド
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- グリコシド
- インドール
- 抗体、モノクローナル
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- ヴィンカアルカロイド
- セコロガニントリプタミンアルカロイド
- インドールアルカロイド
- インドリジジン
- インドリジン
- アントラサイクリン
- ナフテセン
- アミノグリコシド
- 抗体、モノクローナル、マウス由来
- ダウノルビシン
- リツキシマブ
- シクロホスファミド
- ドキソルビシン
- ビンクリスチン
- Pirtobrutinib
その他の研究ID番号
- CLLRT2
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。