Ibrutinib Combined With Rituximab for Treatment of Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies
Phase II, Multi-Center Study to Evaluate the Efficacy and Safety of Ibrutinib Combined With Rituximab for Treatment of Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies
調査の概要
状態
詳細な説明
Recent studies have found that about 30% of DLBCL have mutations in MYD88 and/or CD79A/B genes. MYD88 and CD79A/B protein molecules belong to two signal transduction pathways, which regulate B cell proliferation. Both MYD88 and CD79A/B gene mutations can abnormally activate BTK located downstream of MYD88 and CD79A/B, leading to over activation and proliferation of B cells.
Ibrutinib is the first generation of oral BTKi, which may theoretically inhibit the tumorigenesis of DLBCL with abnormal BTK activation caused by mutations in MYD88 and CD79A/B genes.
A phase II clinical study of ibrutinib monotherapy in the treatment of relapsed and refractory DLBCL showed that the effective rate of ibutinib for single CD79B mutation was 55.5% (5/9 cases), and that for both CD79B and MYD88 mutations was 80% (4/5 cases). About 40 ~ 50% of primary central nervous system large B cell lymphoma (PCNSL) have CD79B and MYD88 mutations. A small sample study found that the overall response rate (ORR) for the treatment of relapsed and refractory PCNSL with ibrutinib was 77% (10/13). An expanded sample study of 44 cases of PCNSL treated with ibrutinib found that the ORR is 52% and progression-free survival (PFS) is 4.8 months. These results suggest that ibrutinib may be more effective in DLBCL with MYD88 and CD79A/B or CD79B mutations.
The relationship between mutations in MYD88 and CD79B and therapeutic sensitivity of ibrutinib can not be simply categorized, because abnormalities in other genes of B cell signaling pathway, such as CARD11, TNFAIP3, CXCR4, JAK1 and PIM1, may also affect the efficacy of ibrutinib. Therefore, it is necessary to comprehensively analyze the gene abnormalities of other B cell related signaling pathways, such as downstream signal of Bruton kinase, CXCR, JAK-STAT, and NFKB, to find out the most effective group of DLBCL patients treated with ibrutinib.
This phase II, single-arm, open-label, multi-center clinical trial will evaluate the efficacy and safety of ibrutinib combined with rituximab in treating relapsed refractory MYD88 and CD79A/B (or CD79B alone) DLBCL who have received at least two prior therapies. The study will also explore the relationship between MYD88 and/or CD79A/B and efficacy, and detect the gene abnormality by Next Generation Sequencing (NGS) and evaluate the relationship between other gene abnormality and efficacy.
研究の種類
入学 (予想される)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：yuankai Shi, M.D.
- 電話番号：86 010-87788293
- メール：syuankaipumc@126.com
研究連絡先のバックアップ
- 名前：Yan Qin, M.D.
- 電話番号：86 13601282738
- メール：qinyan66@vip.sina.com
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:
- Participants must be able to understand and be willing to sign a written informed consent document;
- Men and woman who are at least 18 years of age on the day of consenting to the study;
- According to the WHO 2016 classification criteria, pathologically confirmed CD20+diffuse large B-cell lymphoma;
- Patients with MYD88 and CD79A/B mutations or CD79B alone;
- Relapse or progression after treatment with at least two prior therapies;
- There is at least one measurable lesion, defined as a two-path measurable, intraductal lesion short neck >1.5cm, extranodal lesion short diameter >1.0cm;
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Blood routine examination meets the following criteria:
Neutrophil count ≥ 1.0 x 109 / L; Platelet ≥ 75 x 109 / L; Hemoglobin ≥ 10.0 g / dL;
The main organ function meets the following criteria:
Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value; Bilirubin ≤ 2.0 mg / dL; Creatinine clearance rate ≥ 60 mL / min;
- Must agree to effective contraception
Exclusion Criteria:
- Transformed diffuse large B-cell lymphoma;
- HBV DNA positive or HCV RNA positive;
- Patient is known to have an uncontrolled active systemic infection;
- Left ventricular ejection fraction < 40%;
- Previous autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, dry syndrome, ankylosing spondylitis, etc;
- Immunosuppressive drugs are being or have been used in the past;
- Known hypersensitivity to the study drug or any of its excipients;
- There are other active malignant tumors that may interfere with this study requiring treatment;
- Known history of human immunodeficiency virus (HIV) infection;
- Previous autologous stem cell transplantation or allogeneic hematopoietic stem cell transplantation;
- The investigator judges that the patient has other inappropriate circumstances.
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：Ibrutinib Combined With Rituximab
Induction therapy: Ibrutinib 560mg administered oral once a day of each 21-day cycle for 6 cycles. Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles. Maintenance therapy: Ibrutinib 560mg administered oral once a day of each 56-day cycle for 6 cycles. Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 56-day cycle for 6 cycles. |
Drug: ibrutinib ibrutinib 560mg administered orally once daily. Other Name: Imbruvica Drug: rituximab rituximab 375mg/m² administered intravenously (IV)
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 |
|---|---|---|
|
Objective Response Rate(ORR)
時間枠：24 months after the last patient's enrollment
|
The ORR includes complete response and partial response.
The treatment response assessments are as follows: Evaluation of treatment response are performed every 2 cycles followed the International Lymphoma Collaborative Group guidelines.
|
24 months after the last patient's enrollment
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression Free Survival (PFS)
時間枠：at 6 month and 1 year
|
From the date into this study to disease progression or death
|
at 6 month and 1 year
|
|
Overall Survival (OS)
時間枠：at 6 month and 1 year
|
From the date into this study to death
|
at 6 month and 1 year
|
|
Event Free Survival (EFS)
時間枠：at 6 month and 1 year
|
From the date into this study to disease progression, relapse from CR as assessed by the investigator, completion of study treatment followed by subsequent systemic anti-lymphoma therapy, or death from any cause, whichever occurred first.
|
at 6 month and 1 year
|
|
Adverse events
時間枠：24 months after the last patient's enrollment
|
AEs will be evaluated using the NCI CTCAE v4.0.
|
24 months after the last patient's enrollment
|
|
Assessment of the correlation between MYD88 and/or CD79A/B or other gene abnormality and efficacy.
時間枠：24 months after the last patient's enrollment
|
To explore the relationship between MYD88 and/or CD79A/B and efficacy and to detect the gene abnormality by Next Generation Sequencing (NGS) and evaluate the relationship between other gene abnormality and efficacy.
|
24 months after the last patient's enrollment
|
協力者と研究者
捜査官
- 主任研究者：Yuankai Shi, M.D.、Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
研究記録日
主要日程の研究
研究開始 (予想される)
一次修了 (予想される)
研究の完了 (予想される)
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
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