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
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: yuankai Shi, M.D.
- Número de telefone: 86 010-87788293
- E-mail: syuankaipumc@126.com
Estude backup de contato
- Nome: Yan Qin, M.D.
- Número de telefone: 86 13601282738
- E-mail: qinyan66@vip.sina.com
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: 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)
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Objective Response Rate(ORR)
Prazo: 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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Progression Free Survival (PFS)
Prazo: 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)
Prazo: at 6 month and 1 year
|
From the date into this study to death
|
at 6 month and 1 year
|
|
Event Free Survival (EFS)
Prazo: 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
Prazo: 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.
Prazo: 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
|
Colaboradores e Investigadores
Investigadores
- Investigador principal: Yuankai Shi, M.D., Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Antecipado)
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- NCC2613
Plano para dados de participantes individuais (IPD)
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