無痛性B細胞非ホジキンリンパ腫の被験者におけるリツキシマブと組み合わせたBI-1206の研究
CD32b (FcYRIIB) に対するモノクローナル抗体である BI-1206 の第 1/2a 相臨床試験は、再発またはリツキシマブに抵抗性の無痛性 B 細胞非ホジキンリンパ腫の被験者を対象に、リツキシマブと併用します。
Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab with or without Acalabrutinib in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab
調査の概要
詳細な説明
This is a Phase 1/2a, multicenter, dose escalation, consecutive-cohort, open-label trial of BI-1206 in combination with rituximab with or without acalabrutinib in subjects with indolent relapsed or refractory B-cell NHL, sub-types FL (except FL grade 3B), MZL, and MCL.
Phase 2a, consists of signal seeking cohorts followed by a randomized, parallel, two-arm dose optimization.
The trial consists of 2 main parts:
Phase 1
- Dose Escalation, with two different Arms assessing IV or SC dosing of BI-1206 in combination with rituximab, with dose escalation cohorts and selection of the IV and SC doses of BI-1206 for Phase 2a
Phase 2a
- Dose Expansion, with one expansion cohort evaluating the selected IV dose of BI-1206 in combination with rituximab
- Signal Seeking, assessing IV and SC dosing of BI-1206 in combination with rituximab and acalabrutinib. The Signal Seeking will consist of a Safety Run-in and an Expansion
- Dose Optimization to select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Erika Bågeman
- 電話番号：+46706126618
- メール：erika.bageman@bioinvent.com
研究連絡先のバックアップ
- 名前：Andres McAllister, MD, PhD
- メール：andres.mcallister@bioinvent.com
研究場所
-
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Georgia
-
Atlanta、Georgia、アメリカ、30322
- 積極的、募集していない
- Emory University Hospital
-
-
Kentucky
-
Louisville、Kentucky、アメリカ、40207
- 募集
- Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
-
主任研究者：
- Don Stevens, MD
-
-
-
-
-
Lund、スウェーデン、SE-22185
- 終了しました
- Department of Oncology, Skåne University Hospital
-
-
Sweden
-
Uppsala、Sweden、スウェーデン、751 85
- 終了しました
- Department of Oncology, Academical Hospital
-
-
-
-
-
Barcelona、スペイン
- 募集
- Institut Català d'Oncologia, L'Hospitalet de Llobregat
-
主任研究者：
- Eva Domingo Domenech, MD
-
コンタクト：
-
Madrid、スペイン
- 募集
- University Hospital Fundacion Jimenez Diaz
-
主任研究者：
- Raul Cordoba Mascunano, MD
-
コンタクト：
-
-
Barcelona
-
Badalona、Barcelona、スペイン
- 募集
- Hospital ICO, Trias i Pujol
-
主任研究者：
- Juan Manuel Sancho Cia, MA
-
コンタクト：
-
Barcelona、Barcelona、スペイン
- 募集
- Hospital Universitari Vall d'Hebron
-
主任研究者：
- Pablo Abrisqueta Costa, MD
-
コンタクト：
-
Barcelona、Barcelona、スペイン
- 募集
- Hospital de la Santa Creu i Sant Pau, Dep Hematologia
-
コンタクト：
-
主任研究者：
- Sara Miqueleiz Alamos, MD
-
-
Madrid
-
Madrid、Madrid、スペイン
- 募集
- Hospital Universitario HM Sanchinarro
-
コンタクト：
- Agustín Penedo Coello
- メール：apenedo@hmhospitales.com
-
主任研究者：
- Augustin Penedo Coello, MD
-
Madrid、Madrid、スペイン
- 募集
- Hospital General Universitario Gregorio Marañon-Oncología Médica
-
主任研究者：
- Mariana Bastos Oreiro, MD
-
コンタクト：
-
-
Murcia
-
Murcia、Murcia、スペイン
- まだ募集していません
- Hospital Universitario Virgen de la Arrixaca
-
主任研究者：
- Joaquin Gomez Espuch, MD
-
コンタクト：
-
-
Seville
-
Seville、Seville、スペイン
- 募集
- Hospital University Virgen Macarene
-
主任研究者：
- Sergio Ortegon Alcaide, MD
-
コンタクト：
- Sergio Ortegón Alcaide
- メール：sortegonalcaide@gmail.com
-
-
-
-
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Stuttgart、ドイツ
- 引きこもった
- Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
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Hesse
-
Frankfurt am Main、Hesse、ドイツ
- まだ募集していません
- Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
-
主任研究者：
- Eckhart Weidmann, MD
-
コンタクト：
-
-
-
-
-
Curitiba、ブラジル
- まだ募集していません
- Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
-
コンタクト：
-
主任研究者：
- Eduardo Munhoz, MD
-
Rio de Janeiro、ブラジル
- まだ募集していません
- Ruschel Medicina e Pesquisa Clínica
-
コンタクト：
- Thaiane Alexandre, RN
- メール：thaianealexandre@ruschelmedicina.com.br
-
主任研究者：
- Rony Schaffel, MD
-
São Paulo、ブラジル
- まだ募集していません
- Hospital Samaritano
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コンタクト：
-
主任研究者：
- Carlos Chiattone, MD
-
São Paulo、ブラジル
- まだ募集していません
- Hospital Sírio-Libanês
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主任研究者：
- Ana Rita Da Fonseca, MD
-
コンタクト：
-
São Paulo、ブラジル
- まだ募集していません
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
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コンタクト：
- Camila Hinsching, RN
- メール：camila.f@hc.fm.usp.br
-
主任研究者：
- Juliana Pereira, MD
-
São Paulo、ブラジル
- 募集
- A.C. Camargo Cancer Center
-
主任研究者：
- Ana Costa Cordeiro, MD
-
コンタクト：
-
São Paulo、ブラジル
- まだ募集していません
- Hospital Amaral Carvalho
-
コンタクト：
-
主任研究者：
- Ederson Roberto De Mattos, MD
-
São Paulo、ブラジル
- 募集
- Hospital Israelita Albert Einstein
-
主任研究者：
- Guilherme Perini, MD
-
コンタクト：
-
-
Estado de Bahia
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Salvador、Estado de Bahia、ブラジル
- 募集
- Hospital São Rafael
-
コンタクト：
- Cacilda
- メール：analuziaschriefer@gmail.com
-
主任研究者：
- Ana Luiza Schriefer, MD
-
-
Rio Grande do Sul
-
Porto Alegre、Rio Grande do Sul、ブラジル
- 募集
- Hospital de Clínicas de Porto Alegre
-
主任研究者：
- Laura Maria Fogliatto, MD
-
コンタクト：
- Suellen
- メール：fogliattopesquisa@gmail.com
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-
-
-
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Grudziądz、ポーランド、86-300
- 終了しました
- Szpital Specjlistyczny
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Krakow、ポーランド
- 終了しました
- Małopolskie Centrum Medyczne
-
-
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:
- Are ≥ 18 years of age by initiation of study treatment.
- Have B-cell NHL proven by histology, with histological subtypes limited to follicular lymphoma (FL) (except FL grade 3B), MCL and marginal zone lymphoma (MZL)
- Have measurable nodal disease
- Are willing to undergo lymph node biopsies or biopsies of other involved tissue
- Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists
- Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen
- Have a life expectancy of at least 12 weeks
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Have CD20+ malignancy
- Have hematological and biochemical indices within prespecified ranges
Exclusion Criteria:
-
Have had an allogenic bone marrow or stem cell transplant within 12 months
-
Have presence of active chronic graft versus host disease
-
Have current leptomeningeal lymphoma or compromise of the central nervous system
-
Have transformed lymphoma from a pre-existing indolent lymphoma
-
Have Waldenstrom's Macroglobulinemia or FL grade 3B,
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Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.
-
Have known or suspected hypersensitivity to rituximab or BI-1206
-
Have cardiac or renal amyloid light-chain amyloidosis
-
Have received any of the following:
- Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
- Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
- Immunotherapy within 8 weeks
- Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib
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Have ongoing toxic manifestations of previous treatments.
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Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).
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Have had major surgery from which the subject has not yet recovered.
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Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
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Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
-
Have an active, known or suspected autoimmune disease.
-
Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])
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Have current malignancies of other types
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：非ランダム化
- 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：BI-1206 IV Dose Escalation
Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
他の名前：
|
|
実験的：BI-1206 SC Dose Escalation
Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
他の名前：
|
|
実験的：Phase 2a IV Dose expansion
BI-1206 IV in Combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
他の名前：
|
|
実験的：Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
他の名前：
Acalabrutinib 100 mg orally as per SmPC
他の名前：
|
|
実験的：Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
他の名前：
Acalabrutinib 100 mg orally as per SmPC
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 |
|---|---|---|
|
Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
時間枠：During the 28-day treatment period on induction therapy
|
Assess the safety and tolerability profile of BI-1206 when administered intravenously (IV) or subcutaneously (SC) in combination with rituximab or rituximab and acalabrutinib in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), subtypes follicular lymphoma (FL)(except FL grade 3B), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). Assessment will be done according to National Cancer Institute (NCI-CTCAE) criteria v. 5.0. |
During the 28-day treatment period on induction therapy
|
|
Determining the MTD of BI-1206 at the same dose level experiencing a BI-1206 or Rituximab-related or possibly related dose-limiting toxicity (DLT)
時間枠：During the 28-day treatment period on induction therapy
|
Phase 1: Select the recommended Phase 2 dose (RP2D) by establishing the maximum tolerated dose (MTD) of BI-1206 given once weekly for 4 weeks, via IV infusion or SC injection in combination with rituximab. |
During the 28-day treatment period on induction therapy
|
|
Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
時間枠：During the 28-day treatment period on induction therapy
|
Phase 2a: Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib. |
During the 28-day treatment period on induction therapy
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Evaluation of PK parameters for BI-1206
時間枠：Up to 1 year
|
PK parameters assessed will include AUC, Cmax, time to Cmax and t1/2 of BI-1206 when administered IV or SC |
Up to 1 year
|
|
Evaluation of ADA (immunogenicity) response to BI-1206
時間枠：Up to 1 year
|
Assess the incidence and titre of antidrug antibodies of BI-1206 in serum when administered IV or SC in combination with rituximab or rituximab and acalabrutinib. |
Up to 1 year
|
|
Measurement of peripheral blood B-lymphocytes depletion
時間枠：Up to 1 year
|
Evaluate the effect of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib measuring B Lymphocytes CD19+ (absolute value) as part of hematology assessment to determine the level of peripheral blood B lymphocyte depletion. |
Up to 1 year
|
|
Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).
時間枠：Up to 1 year
|
Assess possible anti-tumor activity of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib at Week 6 after first dose of BI-1206 and for subjects who continue during maintenance therapy. |
Up to 1 year
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Expression levels of CD32b protein
時間枠：Up to 1 year
|
To investigate CD32b protein expression levels using flow cytometry to evaluate any potential correlation with clinical responses. Change from baseline expression levels will be summarized descriptively by dose cohort and/or response to treatment. |
Up to 1 year
|
|
Assessment of Patient Reported Outcomes using the NCI PRO-CTCAE questionnaire
時間枠：Up to 1 year
|
The NCI PRO-CTCAE will be used to evaluate symptomatic toxicities reported by patients. The questionnaire characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities, all toxicities that can be meaningfully reported from the patient perspective. Responses are scored from 0 to 4 (or 0/1 for absent/present). Scores for each attribute (frequency, severity and/or interference) will be presented descriptively (e.g. summary statistics or graphical presentations). |
Up to 1 year
|
|
Expression levels of CD32b and/or other immunological markers
時間枠：Up to 1 year
|
Perform whole-transcriptome, quantitative polymerase chain reaction (qPCR) and/or IHC analysis of lymph node biopsies to evaluate potential correlation with clinical responses. |
Up to 1 year
|
|
Measurement of serum cytokines levels and/or soluble CD32b.
時間枠：Up to 1 year
|
Study the potential cause of infusion related reactions (IRRs), such as cytokine release signs, C-reactive protein (CRP) and/or soluble CD32b. |
Up to 1 year
|
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
その他の研究ID番号
- 17-BI-1206-02
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
All information concerning the product as well as any matter concerning the operation of the Sponsor, such as clinical indications for the drug, its formula, methods of manufacture and other scientific data relating to it, that have been provided by the Sponsor and are unpublished, are confidential and must remain the sole property of the Sponsor. The Investigator will agree to use the information only for the purposes of carrying out this study and for no other purpose unless prior written permission from the Sponsor is obtained.
IPD 共有時間枠
Within one year from end of study
IPD 共有アクセス基準
Paper copy of CSR
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- CSR
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。