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

NCT03752138 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: 2018-0495NCI-2018-02667P30CA016672
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  Will be tabulated with frequency and percentage by grade, attribution to treatment, and by dose level/schedule.

  Up to 30 days

• Response rate

  Will be estimated alone with 95% confidence interval.

  Up to 30 days

• Overall survival

  Will be estimated using the Kaplan-Meier method.

  Up to 1 year

• Disease free survival

  Will be estimated using the Kaplan-Meier method.

  Up to 1 year

• Duration of disease control

  Will be estimated using the Kaplan-Meier method.

  Up to 1 year

Study Arms (5)

Group 1 Part 1 TK216: Days 1-7

EXPERIMENTAL

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

Drug: Group 1: TK216

Group 2 Part 1 TK216: Days 1-7 and 15-28

EXPERIMENTAL

Patients receive TK216 IV on days 1-7 and 15-21 every 28 days.

Drug: Group 2: TK216

Part 2 TK216 + Decitabine 10mg/m2

EXPERIMENTAL

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

Drug: Part 2: Decitabine 10mg/m2; Drug: Part 2: TK216

Part 2 TK216 + Decitabine 20 mg/m2

EXPERIMENTAL

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

Drug: Part 2: Decitabine 20 mg/m2; Drug: Part 2: TK216

Expansion Phase: TK216 + Decitabine

EXPERIMENTAL

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

Drug: Expansion Phase TK216; Drug: Expansion Phase Decitabine

Interventions

Group 1: TK216 DRUG

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

Group 1 Part 1 TK216: Days 1-7

Group 2: TK216 DRUG

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

Also known as: TK-216, TK216

Group 2 Part 1 TK216: Days 1-7 and 15-28

Part 2: Decitabine 10mg/m2 DRUG

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

Also known as: Dacogen

Part 2 TK216 + Decitabine 10mg/m2

Part 2: Decitabine 20 mg/m2 DRUG

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

Also known as: Dacogen

Part 2 TK216 + Decitabine 20 mg/m2

Expansion Phase TK216 DRUG

Expansion cohort will receive the RP2D of TK216

Expansion Phase: TK216 + Decitabine

Expansion Phase Decitabine DRUG

Expansion cohort will receive the RP2D of Decitabine

Also known as: Dacogen

Expansion Phase: TK216 + Decitabine

Part 2: TK216 DRUG

Recommended dose from Part 1.

Part 2 TK216 + Decitabine 10mg/m2; Part 2 TK216 + Decitabine 20 mg/m2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Tapan Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: March 31, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: May 6, 2019

Record last verified: 2019-05