Full-course Immunotherapy Combined With Chemotherapy in Newly Diagnosed B-cell Acute Lymphoblastic Leukemia (FLOW)
This is a single-arm, prospective, phase 2 clinical trial evaluating the improvement of survival outcomes of blinatumomab combined with chemotherapy as a full-course treatment regimen in patients with newly diagnosed Philadelphia chromosome-negative (Ph-negative) B-cell precursor acute lymphoblastic leukemia (B-ALL). The study adopts a "reduced-dose chemotherapy + full-course immunotherapy" strategy: induction therapy with reduced-dose chemotherapy combined with blinatumomab to improve remission rate and tolerability; consolidation therapy with alternating Hyper-CVAD (A/B) regimen，blinatumomab and sequential CD19-directed CAR-T therapy to deepen minimal residual disease (MRD) clearance; allogeneic hematopoietic stem cell transplantation (allo-HSCT) for some patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence); and no maintenance therapy.
The primary endpoint is 2-year relapse-free survival (RFS). Secondary endpoints include 2-year overall survival (OS), the proportion and time to achieve complete response (CRc), and the proportion and time to achieve minimal residual disease (MRD) negativity.
The trial plans to enroll 101 patients aged 15-65 years to demonstrate improved survival outcomes compared with historical controls .
Visão geral do estudo
Status
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Jing Lu Doctor
- Número de telefone: 86+0512-67781137
- E-mail: gloriajlu@163.com
Locais de estudo
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Jiangsu
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Suzhou, Jiangsu, China, 215000
- Recrutamento
- The First Affiliated Hospital of Soochow University
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Contato:
- Jing Lu
- Número de telefone: 86+0512-67781137
- E-mail: gloriajlu@163.com
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Age ≥15 years and ≤65 years.
- Newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) according to WHO diagnostic criteria, with CD19 expression ≥ 20%
- De novo patients with no prior induction therapy (excluding hydroxyurea and corticosteroid use for ≤ 5 days)
- ECOG performance status score 0-3.
- Liver function: Total bilirubin ≤ 3 times the upper limit of normal (ULN); alanine transaminase (ALT) ≤ 3×ULN; aspartate transaminase (AST) ≤ 3×ULN; (leukemic infiltration is excluded).
- Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/min
- Able to understand and voluntarily participate in the study, and provide written informed consent
Exclusion Criteria:
- Philadelphia chromosome-positive (Ph+, BCR-ABL1+) ALL
- T-cell acute lymphoblastic leukemia
- Mature B-cell leukemia/lymphoma, B-cell lymphoblastic lymphoma, extramedullary invasion
- Acute mixed phenotype acute leukemia (MPAL)
- Central nervous system (CNS) leukemia
- HIV infection
- Positive HBV-DNA or HCV-RNA
- New York Heart Association (NYHA) functional class ≥ II, or other conditions deemed unsuitable for enrollment by the investigator
- Pregnant or lactating patients
- Patients who refuse to enroll in the study
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 |
|---|---|
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Experimental: Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation.
Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
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Induction phase: 9 µg/day on days 8-14, 28 µg/day on days 15-21; If D22 BM not CR/CRi, continue Blinatumomab for next 2 weeks of 28 µg/day; Consolidation phase: 28 µg/day for 28 days.
Reduced-dose induction regimen: Idarubicin 8 mg/m², intravenous, day 1; Vindesine 3 mg/m² (max 4 mg), intravenous, day 1; Dexamethasone 9 mg/m²/day, intravenous, days 1-7. Combined with blinatumomab Alternating intensive consolidation chemotherapy: Hyper-CVAD-A: Cyclophosphamide ,Vincristine , Doxorubicin , Dexamethasone ; Hyper-CVAD-B: Methotrexate , Cytarabine . Alternated with CD19-CART and blinatumomab
Allogeneic hematopoietic stem cell transplantation, performed after consolidation therapy in patients with KMT2A rearrangement, TP53 mutation, persistent MRD positivity or MRD recurrence
CD19-CART is administered sequentially in the consolidation phase: First infusion : Following the first course of blinatumomab (28 µg/day, IV, days 1-28) before subsequent Hyper-CVAD chemotherapy. Second infusion : After completion of alternating Hyper-CVAD and blinatumomab consolidation cycles. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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2-year relapse-free survival (RFS)
Prazo: From enrollment through 2 years post-last patient enrolled
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Defined as the time from enrollment to relapse, death from any cause, or last follow-up, whichever occurs first.
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From enrollment through 2 years post-last patient enrolled
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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2-year overall survival (OS)
Prazo: From enrollment through 2 years post-last patient enrolled
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Defined as the time from enrollment to death from any cause or last follow-up, whichever occurs first.
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From enrollment through 2 years post-last patient enrolled
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Composite Complete Remission (CR/CRi) Rate after Induction Therapy
Prazo: From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Proportion of patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction phase.CRc is evaluated at: 1) Day 22 after initial induction therapy; 2) After re-induction with blinatumomab for 2 weeks (for patients not achieving CRc at Day 22)
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From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Minimal Residual Disease (MRD) Negativity Rate
Prazo: From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Proportion of patients achieving MRD negativity (detected by next-generation sequencing, NGS, sensitivity ≥10-⁵) at multiple time points: after first Hyper-CVAD-B chemotherapy, after second Hyper-CVAD-B chemotherapy, and after CD19-CART2 therapy.
MRD negativity is defined as <10-⁵ leukemic blasts in bone marrow.
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From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Suning Chen, The First Affiliated Hospital of Soochow University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
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
Termos MeSH relevantes adicionais
- Neoplasias
- Doenças do sistema imunológico
- Infecções
- Doenças Virais
- Neoplasias por Tipo Histológico
- Infecções por vírus de DNA
- Doenças Linfáticas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Linfoma Não-Hodgkin
- Linfoma de Células B
- Linfoma
- Infecções pelo vírus Epstein-Barr
- Infecções Herpesviridae
- Infecções por Vírus Tumorais
- Doenças hemic e linfáticas
- Linfoma de Burkitt
- Técnicas de investigação
- Terapêutica
- Terapia medicamentosa
- Terapia biológica
- Técnicas imunológicas
- Imunomodulação
- Indução de remissão
- Transferência adotiva
- Imunização, passiva
- Imunização
- Imunoterapia
- blinatumomab
- Quimioterapia de indução
- Imunoterapia, adotiva
- Protocolo CVAD
Outros números de identificação do estudo
- ALL-03
Plano para dados de participantes individuais (IPD)
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