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CD19 Sequential CD22 In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

4 de novembro de 2026 atualizado por: Liping Dou

A Single-Arm, Dose-Escalation Clinical Study on the Safety of CD19 Sequential CD22 In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

This is a single-center, open-label, single-arm, prospective, investigator-initiated dose-escalation study to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of an in vivo CAR-T cell immunotherapy targeting CD19 sequentially followed by CD22, in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The investigational product is a targeted lentiviral vector that transduces the patient's endogenous T/NK cells in situ; no leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is required. Participants receive an intravenous infusion of CD19-targeted in vivo CAR-T on Day 0, followed by an intravenous infusion of CD22-targeted in vivo CAR-T on Day 7. Before the Day 7 infusion, the investigator will assess each participant to determine whether the second infusion should proceed, based on: (i) the proportion of CAR-positive T/NK cells in peripheral blood, which reflects the success of in vivo transduction and early expansion after the first infusion; (ii) the maximum grade and current control of adverse events occurring after the first infusion, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); and (iii) the participant's general condition, including Eastern Cooperative Oncology Group (ECOG) performance status and vital organ function (cardiac, hepatic, renal, pulmonary, and coagulation). The second infusion will be postponed or cancelled if any of these assessments indicates that the risk outweighs the benefit, for example grade >=3 CRS or grade >=2 ICANS that has not resolved to grade <=1, or investigator-judged deterioration in organ function. Dose escalation follows a traditional 3+3 design with planned dose levels of 1×10^9, 3×10^9, and 6×10^9 transducing units (TU), guided by dose-limiting toxicities (DLTs) assessed during Days 0-28; higher dose levels may be explored if the maximum tolerated dose is not reached. Treatment-emergent adverse events and serious adverse events, including CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, and organ toxicity, will be assessed. Preliminary antitumor activity will be evaluated by objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), and the expansion and persistence of in vivo-generated CAR-T cells in peripheral blood will also be evaluated.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This is a single-center, single-arm, open-label, prospective, investigator-initiated clinical study of CD19 sequential CD22 in vivo CAR-T cell immunotherapy in adults with R/R B-ALL whose tumor cells express CD19 and CD22. The investigational product is an engineered lentiviral vector in which the receptor-binding domain of the viral envelope has been mutated to abolish its native pantropic infectivity, and a targeting module composed of an anti-CD7 nanobody (VHH) and a T/NK-cell-specific ligand (CD58 extracellular domain) has been incorporated into the envelope, enabling specific transduction of circulating T cells and NK cells in situ and expression of a CAR directed against CD19 (first infusion) or CD22 (second infusion); no leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is required. Treatment consists of an intravenous infusion of CD19-targeted in vivo CAR-T on Day 0 and an intravenous infusion of CD22-targeted in vivo CAR-T on Day 7. Before the second infusion, the investigator will assess each participant to determine whether the second infusion should proceed, based on: (i) the proportion of CAR-positive T/NK cells in peripheral blood, used to evaluate the efficiency of in vivo transduction and early expansion after the first infusion; (ii) the maximum grade, current grade, and response to management of CRS, ICANS, and other adverse events occurring after the first infusion; and (iii) general condition, including ECOG performance status, vital organ function (cardiac, hepatic, renal, pulmonary, and coagulation), and infection status. Participants who meet the criteria for continued dosing will receive the second infusion as planned. The second infusion will be postponed if grade >=3 CRS or grade >=2 ICANS occurs and does not resolve to grade <=1, or if the investigator judges that continued dosing carries a risk exceeding the potential benefit; if the participant does not recover to a state permitting dosing within the prespecified window, the second infusion will be cancelled and the participant will continue protocol-specified safety follow-up and efficacy assessment. Three dose levels are planned (1×10^9, 3×10^9, and 6×10^9 TU) using a traditional 3+3 escalation design, and the DLT observation window is Days 0-28 after treatment; upon completion of DLT observation at the highest planned dose level without reaching the maximum tolerated dose (MTD), the investigator may explore higher dose levels based on accumulated safety and pharmacodynamic data. Planned enrollment is 12 participants. The study includes a screening period (within 28 days), a treatment period, and a follow-up period of up to 24 months. Safety assessments include adverse events and serious adverse events graded per NCI CTCAE v5.0, with CRS and ICANS graded per the ASTCT consensus criteria; hematologic toxicity, infection, organ toxicity, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), tumor lysis syndrome (TLS), and viral shedding (peripheral blood, saliva, and urine) are also monitored. Disease response is assessed by bone marrow morphology and multiparameter flow cytometry (CR and CRi), with measurable residual disease (MRD) assessed in bone marrow and cerebrospinal fluid. Exploratory cellular kinetics include peripheral blood CAR transgene copies (qPCR) and CAR-positive cell counts, with sampling planned on Days 2, 4, 6, 8, 10, 12, 14, 17, 21, 24, and 28 and at Months 2, 3, 6, 9, and 12 after infusion, and derivation of peak expansion (Cmax), time to peak (Tmax), and the area under the curve from Day 0 to Day 28 (AUC0-28d). Because the investigational product is an integrating lentiviral vector, participants will be enrolled in a long-term safety follow-up program for the detection of delayed adverse events, in accordance with the applicable guidance on gene therapy products; the duration, schedule, and responsible parties are specified in the protocol.

Tipo de estudo

Intervencional

Inscrição (Estimado)

12

Estágio

  • Fase 1

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.

Contato de estudo

Locais de estudo

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100853
        • Recrutamento
        • Chinese PLA General Hospital
        • Contato:

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

14 anos a 75 anos (Filho, Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Voluntarily agrees to participate in the study, has signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
  • Diagnosis of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) according to the World Health Organization (WHO) classification, confirmed by bone marrow aspirate morphology, flow cytometry, or histopathology, with tumor cells shown by immunophenotyping or flow cytometry to express CD19 and CD22. Relapsed/refractory B-ALL is defined as meeting at least one of the following four criteria:

Relapse within 6 months after first remission; Primary refractory disease: failure to achieve complete remission after 2 cycles of standard chemotherapy; Failure to achieve complete remission or relapse after one or more lines of salvage chemotherapy; Relapse after hematopoietic stem cell transplantation.

  • Male or female participants aged 14 to 75 years, inclusive.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Estimated life expectancy of more than 3 months from the date of signing the informed consent form.
  • Adequate renal, hepatic, cardiac, and pulmonary function, defined as follows:

Creatinine clearance (estimated by the Cockcroft-Gault formula) ≥60 mL/min or serum creatinine ≤1.5 × the upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN), total bilirubin≤1.5×ULN; Cardiac ejection fraction≥50%, no pericardial effusion on echocardiography, and no significant abnormalities on electrocardiogram (ECG); No clinically significant pleural effusion, and oxygen saturation >92% on room air at baseline.

  • Participants of reproductive potential must agree to use highly effective contraception before enrollment and for at least 12 months after SL1CC infusion. A negative serum pregnancy test is required for women of childbearing potential at screening. Participants must immediately notify the investigator if pregnancy occurs or is suspected.

Exclusion Criteria:

  • The patient has severe cardiac dysfunction, or left ventricular ejection fraction (LVEF) <50%, or a history within the 12 months prior to enrollment of myocardial infarction, coronary angioplasty or coronary stent implantation, unstable angina, clinically significant arrhythmia, or other severe cardiovascular diseases.
  • A history of severe pulmonary disease associated with impaired lung function.
  • Concurrent progressive malignancy other than acute lymphoblastic leukemia.
  • Severe active infection that cannot be effectively controlled, defined as sepsis or an infection with an uncontrolled infectious focus. Participants may be enrolled after the infection has been adequately controlled.
  • Severe autoimmune disease or congenital immunodeficiency.
  • Active hepatitis B or hepatitis C infection, defined as hepatitis B virus DNA (HBV DNA) or hepatitis C virus RNA (HCV RNA) levels above the lower limit of detection.
  • Human immunodeficiency virus (HIV) infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection; has received a live vaccine within 4 weeks, or is anticipated to require a live vaccine during the study period.
  • History of severe immediate hypersensitivity reactions to any drug required in this study, including antibiotics, or to biological products.
  • Prior treatment with any gene therapy product or any in vivo CAR-T therapy, or known pre-existing neutralizing immunity to the lentiviral vector.
  • Active central nervous system (CNS) leukemia or leptomeningeal involvement not controlled after adequate intrathecal therapy; cerebrospinal fluid examination is required during screening.
  • The patient has severe autoimmune disease, congenital immunodeficiency or active autoimmune disease requiring ongoing systemic immunosuppressive treatment, or is currently within the washout period after having received medications that may affect CAR-T cell immunotherapy, or is anticipated to require medications during the study period that may affect CAR-T cell immunotherapy treatment, or active GVHD requiring systemic therapy.
  • Pregnancy or breastfeeding (lactation).
  • The investigator judges that the patient is unlikely to complete all visits and procedures required by the study protocol (including medium- and long-term follow-up visits), such as insufficient willingness of the patient and their family members to participate in the study, refusal to participate, inability of the patient to fully cooperate with the study arrangements, or inadequate compliance on the part of the patient and their family members.
  • Any other severe physical or psychiatric disorder or clinically significant laboratory abnormality that may increase the risk associated with study participation, interfere with the interpretation of study results, or, in the investigator's judgment, make the participant unsuitable for participation 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: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: The experimental group

In Vivo CAR-T Treatment Group - sequential intravenous infusion of CD19-targeted in vivo CAR-T on Day 0, followed by CD22-targeted in vivo CAR-T on Day 7, at one of three planned dose levels (1×10^9, 3×10^9, or 6×10^9 TU) assigned by a traditional 3+3 dose-escalation design; no leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is administered. Before the second infusion, the investigator must assess (i) the proportion of CAR-positive T/NK cells in peripheral blood, (ii) the maximum grade and current control of CRS, ICANS, and other adverse events after the first infusion, and (iii) ECOG performance status and vital organ function, in order to determine whether the second infusion should proceed as planned; the second infusion will be postponed or cancelled in participants with grade >=3 CRS or grade >=2 ICANS that has not resolved to grade <=1. Higher dose levels may be explored if the maximum tolerated dose is not reached.
Medicamento: CD19-Targeted In Vivo CAR-T Injection (first infusion, Day 0); CD22 -Targeted In Vivo CAR-T Injection (second infusion, Day 7)

The investigational products are engineered lentiviral vector-based in vivo gene therapy products. The viral envelope receptor-binding domain has been mutated to abolish native pantropic infectivity, and a targeting module composed of an anti-CD7 nanobody (VHH) and a T/NK-cell-specific ligand (CD58 extracellular domain) has been incorporated into the envelope, enabling specific transduction of circulating T cells and NK cells in situ and expression of a chimeric antigen receptor directed against CD19 (first infusion, Day 0) or CD22 (second infusion, Day 7). No leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is required. Dose escalation follows a traditional 3+3 design with planned dose levels of 1×10^9, 3×10^9, and 6×10^9 transducing units (TU), guided by the occurrence of dose-limiting toxicities (DLTs).

Outros nomes:
  • In vivo CD19/CD22 CAR-T; targeted lentiviral vector for in vivo CAR-T generation

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Safety and Tolerability
Prazo: From the first in vivo CAR-T infusion through 12 months after treatment

DLTs, the number and percentage of participants who experience DLT during the protocol-defined DLT observation period (Days 0-28) after the first in vivo CAR-T infusion.
From the first in vivo CAR-T infusion through 12 months after treatment
Adverse Events
Prazo: From the first in vivo CAR-T infusion through 12 months after treatment

AEs are graded per NCI CTCAE v5.0
From the first in vivo CAR-T infusion through 12 months after treatment
Cytokine Release Syndrome
Prazo: From the first in vivo CAR-T infusion through 12 months after treatment

Cytokine release syndrome (CRS) is graded according to the ASTCT consensus criteria.
From the first in vivo CAR-T infusion through 12 months after treatment
Immune Effector Cell-associated Neurotoxicity Syndrome
Prazo: From the first in vivo CAR-T infusion through 12 months after treatment

immune effector cell-associated neurotoxicity syndrome (ICANS) is graded according to the ASTCT consensus criteria.
From the first in vivo CAR-T infusion through 12 months after treatment

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Objective Response Rate at Prespecified Follow-up Time Points
Prazo: From the first in vivo CAR-T infusion through 24 months after treatment

The objective response rate (ORR) at 1, 2, 3, 6, 9, 12, 18, and 24 months after treatment, defined as the proportion of participants who achieve a complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete remission with incomplete platelet recovery (CRp). The ORR at 3 months after treatment is the key evaluation time point.
From the first in vivo CAR-T infusion through 24 months after treatment
Overall Survival
Prazo: From the first in vivo CAR-T infusion through 24 months after treatment

Overall survival (OS), defined as the time from the first in vivo CAR-T infusion to death from any cause. Participants who are alive at the last follow-up will be censored on the date of their last known survival status.
From the first in vivo CAR-T infusion through 24 months after treatment
Progression-Free Survival
Prazo: From the first in vivo CAR-T infusion through 24 months after treatment

Progression-free survival (PFS), defined as the time from the first in vivo CAR-T infusion to the first documentation of objective disease progression or death from any cause, whichever occurs first.
From the first in vivo CAR-T infusion through 24 months after treatment
Event-Free Survival
Prazo: From the first in vivo CAR-T infusion through 24 months after treatment

Event-free survival (EFS), defined as the time from the first in vivo CAR-T infusion to the first documentation of objective disease progression, relapse, or death from any cause, whichever occurs first.
From the first in vivo CAR-T infusion through 24 months after treatment
Measurable Residual Disease (MRD) Negativity Rate
Prazo: At Day 28 and Months 2, 3, 6, 9, 12, 18, and 24 after the first in vivo CAR-T infusion

The proportion of participants with MRD negativity in bone marrow assessed by multiparameter flow cytometry among participants who achieve CR/CRi, at each prespecified assessment time point.
At Day 28 and Months 2, 3, 6, 9, 12, 18, and 24 after the first in vivo CAR-T infusion
Cellular Kinetics (Pharmacokinetics) of In Vivo-Generated CAR-T Cells (Exploratory)
Prazo: Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion

CAR transgene copy number in peripheral blood (qPCR), peak expansion of CAR-T cells in peripheral blood (Cmax).
Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion
Time to Peak Expansion
Prazo: Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion

Peripheral blood sampling is planned on Days 2, 4, 6, 8, 10, 12, 14, 17, 21, 24, and 28 and at Months 2, 3, 6, 9, and 12 after infusion.
Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion
Area Under The Curve From Day 0 to Day 28
Prazo: Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion

The area under the curve from Day 0 to Day 28 (AUC0-28d).Peripheral blood sampling is planned on Days 2, 4, 6, 8, 10, 12, 14, 17, 21, 24, and 28 and at Months 2, 3, 6, 9, and 12 after infusion.
Through Day 28 for AUC0-28d, Cmax, and Tmax; CAR transgene levels through 12 months after infusion

Colaboradores e Investigadores

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

Patrocinador

Liping Dou

Colaboradores

Hebei Senlang Biotechnology Inc., Ltd.

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 (Real)

1 de setembro de 2026

Conclusão Primária (Estimado)

31 de agosto de 2028

Conclusão do estudo (Estimado)

31 de agosto de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

28 de outubro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

4 de novembro de 2026

Primeira postagem (Real)

10 de novembro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

10 de novembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

4 de novembro de 2026

Última verificação

1 de novembro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 2026-749

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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