TK216 and Decitabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia
Phase I Study of TK216 in Patients With Relapsed and Refractory Leukemias
Visão geral do estudo
Status
Descrição detalhada
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of Ets-family transcription factor inhibitor TK216 (TK216) in patients with relapsed and refractory (R/R) acute myeloid leukemia (AML). (Phase I Dose Escalation) II. To determine the safety and tolerability of TK216 combined with decitabine in patients with relapsed and refractory AML. (Combination Cohort)
SECONDARY OBJECTIVES:
I. Safety profile of TK216 as characterized by adverse event (AE) type, severity, timing and relationship to study drug, as well as laboratory abnormalities in the first and subsequent treatment cycles. (Phase I Dose Escalation) II. To explore the efficacy (complete remission [CR], complete remission without platelet recovery [CRp], complete remission without blood count recovery [CRi], or partial remission [PR]), of TK216 as a single-agent in patients with R/R AML. (Phase I Dose Escalation) III. To assess overall survival (OS), and disease free survival (DFS) in patients with R/R AML treated with TK216. (Phase I Dose Escalation) IV. Duration of disease control defined as first date of disease control identified (either CR/CRp/CRi, PR or SD) until the date of progression. (Phase I Dose Escalation) V. To explore biomarkers of response and resistance in patients with R/R AML treated with TK216. (Phase I Dose Escalation) VI. Safety profile of TK216 in combination with decitabine as characterized by adverse event (AE) type, severity, timing and relationship to study drug, as well as laboratory abnormalities in the first and subsequent treatment cycles. (Combination Cohort) VII. To explore the efficacy (complete remission [CR], complete remission without platelet recovery [CRp], complete remission without blood count recovery [CRi], or partial remission [PR], of TK216 in combination with decitabine in patients with R/R AML. (Combination Cohort) VIII. To assess overall survival (OS), and progression free survival (PFS) in patients with R/R AML treated with TK216 + decitabine. (Combination Cohort) IX. Duration of disease control defined as first date of disease control identified (either CR/CRp/CRi, PR or SD) until the date of progression. (Combination Cohort) X. To explore biomarkers of response and resistance in patients with R/R AML treated with TK216 + decitabine. (Combination Cohort)
OUTLINE: This is a dose-escalation study.
Patients receive TK216 intravenously (IV) continuously on days 1-7 every 21 days, or continuously on days 1-7 and 15-21 every 28 days. Patients also receive decitabine IV over 60 minutes on days 1-10 every 28 days. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Tipo de estudo
Estágio
- Fase 1
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia for which no available standard therapies are indicated or anticipated to result in a durable response
- Patients must not have had leukemia therapy for 14 days prior to starting TK216. However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study
- Bilirubin =< 2 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) -- or =< 5 x ULN if related to leukemic involvement
- Creatinine =< 1.5 x ULN
- Known cardiac ejection fraction of > or = 45% within the past 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol
Exclusion Criteria:
- Pregnant women are excluded from this study because the agent used in this study has the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided
- Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patient with documented hypersensitivity to any of the components of the therapy program
- Patients with active, uncontrolled central nervous system (CNS) leukemia will not be eligible
- Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use at least 1 form of barrier birth control (such as condom) prior to study entry and for the duration of study participation
- Patients with known history of serous retinopathy will not be eligible
- Prior treatment with TK216
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Group 1 Part 1 TK216: Days 1-7
Patients receive TK216 IV continuously on days 1-7 every 21 days.
|
Starting Dose: 288 mg/m2 given by vein on Days 1-7 of a 21 day cycle.
|
|
Experimental: Group 2 Part 1 TK216: Days 1-7 and 15-28
Patients receive TK216 IV on days 1-7 and 15-21 every 28 days.
|
Starting Dose: 144 mg/m2 given by vein on Days 1-7 and 15-21 of a 23 day cycle.
Outros nomes:
|
|
Experimental: Part 2 TK216 + Decitabine 10mg/m2
Patients receive recommended dose of TK216 from Part 1 plus Decitabine.
|
10mg/m2 by vein on Days 1-10 of a 28 day cycle.
Outros nomes:
Recommended dose from Part 1.
|
|
Experimental: Part 2 TK216 + Decitabine 20 mg/m2
Patients receive recommended dose of TK216 from Part 1 plus Decitabine.
|
Recommended dose from Part 1.
20 mg/m2 by vein on Days 1-10 of a 28 dayi cycle.
Outros nomes:
|
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Experimental: Expansion Phase: TK216 + Decitabine
All patients in the expansion cohort will receive the RP2D of TK216 and Decitabine.
|
Expansion cohort will receive the RP2D of TK216
Expansion cohort will receive the RP2D of Decitabine
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of adverse events
Prazo: Up to 30 days
|
Will be tabulated with frequency and percentage by grade, attribution to treatment, and by dose level/schedule.
|
Up to 30 days
|
|
Response rate
Prazo: Up to 30 days
|
Will be estimated alone with 95% confidence interval.
|
Up to 30 days
|
|
Overall survival
Prazo: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
|
Disease free survival
Prazo: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
|
Duration of disease control
Prazo: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Tapan Kadia, M.D. Anderson Cancer Center
Publicações e links úteis
Links úteis
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
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2018-0495 (Outro identificador: M D Anderson Cancer Center)
- P30CA016672 (Concessão/Contrato do NIH dos EUA)
- NCI-2018-02667 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
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