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Ruxolitinibe para o tratamento de leucemia linfocítica granular grande de células T

30 de setembro de 2026 atualizado por: Jonathan Brammer

Um estudo de fase II avaliando a eficácia de Ruxolitinibe em pacientes com leucemia linfocítica granular grande de células T (T-LGLL)

This phase II trial tests whether ruxolitinib works to shrink tumors in patients with T-cell large granular lymphocyte leukemia. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

PRIMARY OBJECTIVE:

I. Determine the overall response rate (ORR) of ruxolitinib in patients with T-cell large granular lymphocytic leukemia (T-LGLL) as compared to historical controls.

SECONDARY OBJECTIVES:

I. Rate of conversion from PR at 4 months to CR at 8 and 12 months (at full ruxolitinib dosage).

II. Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance) at 4, 8, 12 months.

III. Incidence of grade III/IV toxicities (at full ruxolitinib dosage). IV. Quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Health Assessment Questionnaire Disability Index (HAQDi), and Short Form (SF)-36 questionnaire at baseline, 5 months, and every 6 months during response follow up for up to 12 months.

EXPLORATORY OBJECTIVE:

I. Objective benefit (OB) rate at 4 months defined as a patient that had improvement in their cytopenias, transfusion dependence but not attaining a partial response (PR).

II. Leukemia-free survival III. Progression-free survival

OUTLINE:

Patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients who achieve a response (CR or PR) may receive an additional 12 months of ruxolitinib, for a maximum of 24 months. Additionally, patients undergo blood sample collection throughout study.

Tipo de estudo

Intervencional

Inscrição (Estimado)

30

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.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Estados Unidos
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02215
    • New York
      • New York, New York, Estados Unidos, 10065
        • Recrutamento
        • Memorial Sloan Kettering Cancer Center
        • Contato:
        • Investigador principal:
          • Alison Moskowitz, MD
    • Ohio
      • Columbus, Ohio, Estados Unidos, 43210
        • Recrutamento
        • Ohio State University Comprehensive Cancer Center
        • Investigador principal:
          • Jonathan Brammer, MD
        • 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

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

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Age 18 or older and able to swallow pills

  • Diagnosis of T-LGLL defined as: LGL cell population meeting diagnostic criteria (defined as CD3+CD8+ cell population >650/mm3 or CD3+CD8+CD57+ population >500/mm3 or LGL cell population with other immunophenotype that includes co-expression of CD3+, CD8+, CD57+ with >500 cells/mm3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis or relapse). This also includes patients with rare T-LGLL variants include CD4+ T-LGLL, and gamma/delta T-LGLL which can be CD4- and CD8-), though patients still must have the presence of a clonal T-cell receptor within 1 month of diagnosis or relapse. Note: patients with MDS-like T-LGLL may be included with PI approval even if CD3+CD8+ cell population is < 650/mm^3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm^3

  • Untreated T-LGLL or failed at least one line of frontline therapy;

  • Patients must be off treatment for at least 14 days or 5 half-lives, whichever is longer

  • Require Treatment for T-LGLL (one or more required)

    • Symptomatic anemia with hemoglobin < 10 g/dL
    • Transfusion-dependent anemia
    • Neutropenia with absolute neutrophil count (ANC) < 500/mm^3
    • Neutropenia with ANC < 1500/mm^3 with recurrent infections

  • Platelet count > 50 x 10^9/L. Platelet transfusion may be utilized to meet inclusion criteria, as long as the platelet count remains >50,000/uL within 5 days of last transfusion. Note: Patients with platelets <100 x 109/L and renal impairment are not permitted to enroll to the study. Renal impairment is defined as creatinine clearance (CrCl) < 90 mL/min.

  • Serum creatinine =< 2 x the upper limit of normal (ULN)

  • - Estimated glomerular filtration rate (eGFR) => 30 mL/min using the Modification of Diet in Renal Disease (MDRD) equation (multiplying eGFR by each subjects Body Surface Area [BSA])

  • Total bilirubin =< 1.5 x ULN (patients with Gilbert's syndrome with a bilirubin > 1.5 x ULN permitted)

  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

  • Alkaline phosphatase (ALP) =< 2.5 x ULN

  • Eastern cooperative oncology group (ECOG) performance status =< 2

  • Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study treatment until 5 half-lives have passed. Male subject agrees to use an acceptable method for contraception for the duration of the study treatment until 5 half-lives have passed.

  • Able to sign informed consent

Exclusion Criteria:

  • Absolute neutrophil count (ANC) less than 100/mm^3. Note: granulocyte colony-stimulating factor (G-CSF) may be utilized to enable patients to meet inclusion criteria, as long as the ANC remains above 100/mm^3 for 5 days after administration of last growth-factor.
  • Active infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded. Patients with tuberculosis risk factors will be required to undergo quantiferon testing and/or purified protein derivative (PPD) testing with a negative result prior to entering the study.
  • Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat LGLL symptoms, but must be weaned within one month of initiation of trial drug). Patients on stable, chronic prednisone =< 10 mg for rheumatologic/autoimmune conditions are exempted from this requirement. They may enroll on the study
  • Active, concurrent malignancy unless deemed related to T-LGLL by principal investigator (PI). Early stage skin cancers, prostate cancer, permitted if under no active therapy
  • For females of childbearing potential: Positive pregnancy test or lactating
  • Unstable angina or myocardial infarction within the past 2 months
  • Chronic obstructive pulmonary disease or other interstitial lung disease in active exacerbation
  • Cirrhosis
  • For any strong CYP3A4 inhibitors deemed a moderate or severe risk of interaction with ruxolitinib, a wash-out period of 14 days, or 5 half-lives, whichever is longer, is needed prior to starting ruxolitinib
  • Given the CYP3A4 inhibition potential of grapefruit, grapefruit juice, Seville orange juice, pomelos, and starfruits, patients will need to refrain from these foods/drinks for 14 days prior to initiation of therapy, and throughout the study period

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: Treatment (ruxolitinib)

Patients receive ruxolitinib PO BID on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients who achieve a response (CR or PR) may receive an additional 12 months of ruxolitinib, for a maximum of 24 months.
Medicamento: Ruxolitinib

Given PO

Outros nomes:
  • Jakafi
  • INCB-18424
  • INCB18424
  • Inibidor oral de JAK INCB18424

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Overall response rate (ORR)
Prazo: Up to 12 months

The ORR will be calculated as the proportion of patients who achieve a response to therapy divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least four months of therapy with ruxolitinib. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed). Additional outcomes including rates of conversion from PR at 4 months to CR at 8 and 12 months on full dose ruxolitinib, and rate of molecular remission (TCR clearance, STAT3 mutation clearance) at 4, 8, 12 months on full dose ruxolitinib will also be reported as proportions with 95% binomial CIs.
Up to 12 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Incidence of treatment-emergent adverse events
Prazo: Up to 12 months

Treatment-emergent adverse events will be reported overall and by toxicity grade.
Up to 12 months
Leukemia-free survival (LFS)
Prazo: From first response until disease progression, death, or censoring (if alive and disease-free at the end of follow-up), assessed up to 12 months

Kaplan Meier curves will be generated and the median LFS and 95% CIs will be reported.
From first response until disease progression, death, or censoring (if alive and disease-free at the end of follow-up), assessed up to 12 months
Patient quality-of-life (QOL) EORTC
Prazo: Up to 12 months

Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Up to 12 months
Patient quality-of-life (QOL) QLQ-C30
Prazo: Up to 12 months

Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Up to 12 months
Patient quality-of-life (QOL) HAQDi
Prazo: Up to 12 months

Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Health Assessment Questionnaire-Disability Index questionnaires given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Up to 12 months
Patient quality-of-life (QOL) SF-36
Prazo: Up to 12 months

Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Short Form-36 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Up to 12 months

Colaboradores e Investigadores

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

Patrocinador

Jonathan Brammer

Investigadores

  • Investigador principal: Jonathan Brammer, MD, Ohio State University Comprehensive Cancer Center

Publicações e links úteis

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Links úteis

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)

3 de maio de 2023

Conclusão Primária (Estimado)

31 de julho de 2027

Conclusão do estudo (Estimado)

31 de julho de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

18 de abril de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de outubro de 2022

Primeira postagem (Real)

24 de outubro de 2022

Atualizações de registro de estudo

Última Atualização Postada (Real)

1 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

30 de setembro de 2026

Última verificação

1 de fevereiro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • OSU-21336
  • NCI-2022-02385 (Identificador de registro: CTRP (Clinical Trial Reporting Program))

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

Sim

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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