TK216 and Decitabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-31

Study Completion Date

2020-12-31

Brief Summary

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This phase I trial studies the side effects and best dose of TK216 and decitabine when given together in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as TK216 and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

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Detailed Description

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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.

Conditions

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Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 Part 1 TK216: Days 1-7

Patients receive TK216 IV continuously on days 1-7 every 21 days.

Group Type EXPERIMENTAL

Group 1: TK216

Intervention Type DRUG

Starting Dose: 288 mg/m2 given by vein on Days 1-7 of a 21 day cycle.

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.

Group Type EXPERIMENTAL

Group 2: TK216

Intervention Type DRUG

Starting Dose: 144 mg/m2 given by vein on Days 1-7 and 15-21 of a 23 day cycle.

Part 2 TK216 + Decitabine 10mg/m2

Patients receive recommended dose of TK216 from Part 1 plus Decitabine.

Group Type EXPERIMENTAL

Part 2: Decitabine 10mg/m2

Intervention Type DRUG

10mg/m2 by vein on Days 1-10 of a 28 day cycle.

Part 2: TK216

Intervention Type DRUG

Recommended dose from Part 1.

Part 2 TK216 + Decitabine 20 mg/m2

Patients receive recommended dose of TK216 from Part 1 plus Decitabine.

Group Type EXPERIMENTAL

Part 2: Decitabine 20 mg/m2

Intervention Type DRUG

20 mg/m2 by vein on Days 1-10 of a 28 dayi cycle.

Part 2: TK216

Intervention Type DRUG

Recommended dose from Part 1.

Expansion Phase: TK216 + Decitabine

All patients in the expansion cohort will receive the RP2D of TK216 and Decitabine.

Group Type EXPERIMENTAL

Expansion Phase TK216

Intervention Type DRUG

Expansion cohort will receive the RP2D of TK216

Expansion Phase Decitabine

Intervention Type DRUG

Expansion cohort will receive the RP2D of Decitabine

Interventions

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Group 1: TK216

Starting Dose: 288 mg/m2 given by vein on Days 1-7 of a 21 day cycle.

Intervention Type DRUG

Group 2: TK216

Starting Dose: 144 mg/m2 given by vein on Days 1-7 and 15-21 of a 23 day cycle.

Intervention Type DRUG

Part 2: Decitabine 10mg/m2

10mg/m2 by vein on Days 1-10 of a 28 day cycle.

Intervention Type DRUG

Part 2: Decitabine 20 mg/m2

20 mg/m2 by vein on Days 1-10 of a 28 dayi cycle.

Intervention Type DRUG

Expansion Phase TK216

Expansion cohort will receive the RP2D of TK216

Intervention Type DRUG

Expansion Phase Decitabine

Expansion cohort will receive the RP2D of Decitabine

Intervention Type DRUG

Part 2: TK216

Recommended dose from Part 1.

Intervention Type DRUG

Other Intervention Names

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TK-216 TK216 Dacogen Dacogen Dacogen

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No