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Clinical Study of Venetoclax Combined With Azacytiside in the Treatment of Myelodysplastic/Myeloproliferative Neoplasms in Adults

7 de março de 2022 atualizado por: Chen Suning, The First Affiliated Hospital of Soochow University

A Multi-center, Phase II, Single-arm Clinical Study of Venetoclax Combined With Azacytiside in the Treatment of Myelodysplastic/Myeloproliferative Neoplasms in Adults

To explore the efficacy of venetoclax combined with azacytidine in Myelodysplastic / myeloproliferative neoplasms（MDS/MPN）, so as to improve the overall survival and treatment status of MDS/MPN patients.

Visão geral do estudo

Status

Inscrevendo-se por convite

Condições

Intervenção / Tratamento

Descrição detalhada

At present, there is no standardized treatment strategy for MDS/MPN. The purpose of our study is to explore the efficacy of venetoclax combined with azacytidine in the treatment of MDS/MPN, so as to improve the overall survival and treatment status of patients with MDS/MPN. After the participants were treated with four cycles of venetoclax combined with azacytidine, the efficacy was evaluated according to the 2015 adult MDS/MPN response criteria to determine the disease status. Participants with disease progression and intolerance withdrew from the study during treatment.

Tipo de estudo

Intervencional

Inscrição (Antecipado)

33

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215000
        • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Male or female, Age (years) >= 18；

  2. Patients newly diagnosed or previously treated with MDS/MPNs (CMML, MDS/MPN-U, aCML) according to 2016 WHO diagnostic criteria:

    Initial diagnosis: CMML: CPSS-mol intermediate risk 2 and above; aCML; MDS/MPN-U.

    Previous treatment: HMA treatment failed.

  3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
  4. Liver function: Total bilirubin ≤3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≤3 ULN; alanine aminotransferase (ALT)≤3 ULN；
  5. Renal function#Ccr ≥30 ml/min;
  6. Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.

Exclusion Criteria:

  1. Acute myeloid leukemia
  2. Myelodysplastic syndrome
  3. Subjects who had previously been treated with Venetoclax
  4. Subjects who are known to be allergic to ingredients of the study drug or their analogues
  5. HIV infection
  6. HBV-DNA or HCV-RNA positive
  7. Subjects with grade 2 or above cardiac failure and those considered unsuitable for inclusion by the investigator
  8. Subjects who are pregnant or breastfeeding
  9. Subjects reject to participate in the study

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Prevenção
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Treatment regime
On day 1 of each cycle, decitabine 75 mg/m2 will be given subcutaneously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 14 day cycle is finished.
Medicamento: venetoclax combined with azacitidine
On day 1 of each cycle, decitabine 75 mg/m2 will be given subcutaneously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 14 day cycle is finished.
Outros nomes:
  • combination of venetoclax plus azacitidine

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Overall Response Rate (ORR)
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years

ORR (equals the rates of complete remission [CR]+partial remission [PR]+complete cytogenetic remission [CCyR]+marrow response [MR[+clinical benefit [CB] )of venetoclax in combination with azacitidine.

  1. CR and CCyR are shown in the secondary outcome measures below.
  2. PR: Normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts (and blast equivalents) reduced by 50%, but remaining>5% of cellularity except in cases of MDS/MPN with≤5% bone marrow blasts at baseline.

  3. MR: Optimal marrow response: Presence of all marrow criteria necessary for CR without normalization of peripheral blood indices.

    Partial marrow response: Bone marrow blasts (and blast equivalents) reduced by 50%, but remaining>5% of cellularity, or reduction in grading of reticulin fibrosis from baseline on at least 2 bone marrow evaluations spaced at least 2 months apart.

  4. CB: Hematology improvement, spleen response and symptom response.
Study start date to study end date, or death, whichever comes first, up to 4 years

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Complete remission rate
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
  1. Bone marrow: ≤5% myeloblasts (including monocytic blast equivalent in case of CMML) with normal maturation of all cell lines and return to normal cellularity Osteomyelofibrosis absent or equal to "mild reticulin fibrosis" (≤grade 1 fibrosis).
  2. Peripheral blood: Leukocyte≤10×10E9 cells/L; Hemoglobin≥11g/dL; Platelets≥100×10E9/L, ≤450×10E9/L; Neutrophils≥1.0×10E9/L; Blasts 0%; Neutrophil precursors reduced to≤2%; Monocytes ≤1.0× 10E9/L.
  3. Extramedullary disease: Complete resolution of extramedullary disease present before therapy (eg, cutaneous disease, disease-related serous effusions), including palpable hepatosplenomegaly.
Study start date to study end date, or death, whichever comes first, up to 4 years
Complete remission rate of bone marrow morphology
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
Presence of all marrow criteria necessary for CR without normalization of peripheral blood indices as presented above.
Study start date to study end date, or death, whichever comes first, up to 4 years
Hematology improvement (HI) rate
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years

Percentages of participants with HI (erythroid/platelet/neutrophil responses)

  1. Erythroid response: Hemoglobin increase by≥2.0 g/dL; Transfusion independence (TI) for ≥8 week for patients requiring at least 4 packed red blood cell transfusions in the previous 8 week; Only red blood cell transfusions given based on physician's judgment for a pretreatment Hgb of ≤8.5 g/dL will count in the red blood cell TI response evaluation.
  2. Platelet response: TI when previously requiring platelet transfusions of at least a rate of 4 platelet transfusions in the previous 8 week; Pretreatment≤20×10E9/L: increase from<20×10E9/L to>20×10E9/L and by at least 100%; Pretreatment>20×10E9/L but≤100×10E9/L: absolute increase of ≥30×10E9/L.
  3. Neutrophil response: Pretreatment≤0.5×10E9/L at least 100% increase and an absolute increase≥0.5×10E9/L; Pretreatment>0.5×10E9/L and≤1.0×10E9/L, at least 50% increase and an absolute increase ≥0.5×10E9/L.
Study start date to study end date, or death, whichever comes first, up to 4 years
Complete cytogenetic remission rate
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
Resolution of previously present chromosomal abnormality (known to be associated with myelodysplastic, syndrome myeloproliferative neoplasms, or MDS/MPN), as seen on classic karyotyping with minimal of 20 metaphases or FISH.
Study start date to study end date, or death, whichever comes first, up to 4 years
Incidence of severe infection (≥grade 3 )
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
Assessed using CTCAE 5
Study start date to study end date, or death, whichever comes first, up to 4 years
Spleen response rate
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
Either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not palpable.
Study start date to study end date, or death, whichever comes first, up to 4 years
Symptom response rate
Prazo: Study start date to study end date, or death, whichever comes first, up to 4 years
Improvement in symptoms as noted by decrease of ≥50% as per the MPN-SAF TSS scoring<20 were not considered eligible for measuring clinical benefit.
Study start date to study end date, or death, whichever comes first, up to 4 years

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

The First Affiliated Hospital of Soochow University

Investigadores

  • Investigador principal: Suning Chen, Professor, The First Affiliated Hospital of Soochow University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Antecipado)

1 de abril de 2022

Conclusão Primária (Antecipado)

1 de agosto de 2022

Conclusão do estudo (Antecipado)

1 de fevereiro de 2023

Datas de inscrição no estudo

Enviado pela primeira vez

21 de fevereiro de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

7 de março de 2022

Primeira postagem (Real)

16 de março de 2022

Atualizações de registro de estudo

Última Atualização Postada (Real)

16 de março de 2022

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de março de 2022

Última verificação

1 de março de 2022

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • MDS/MPN-01

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

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