- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT03752138
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
Studieöversikt
Status
Detaljerad beskrivning
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.
Studietyp
Fas
- Fas 1
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: 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.
|
Experimentell: 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.
Andra namn:
|
Experimentell: 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.
Andra namn:
Recommended dose from Part 1.
|
Experimentell: 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.
Andra namn:
|
Experimentell: 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
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Incidence of adverse events
Tidsram: 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
Tidsram: Up to 30 days
|
Will be estimated alone with 95% confidence interval.
|
Up to 30 days
|
Overall survival
Tidsram: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
Disease free survival
Tidsram: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
Duration of disease control
Tidsram: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
|
Up to 1 year
|
Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Tapan Kadia, M.D. Anderson Cancer Center
Publikationer och användbara länkar
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Förväntat)
Primärt slutförande (Förväntat)
Avslutad studie (Förväntat)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 2018-0495 (Annan identifierare: M D Anderson Cancer Center)
- P30CA016672 (U.S.S. NIH-anslag/kontrakt)
- NCI-2018-02667 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
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