<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03752138</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0495</org_study_id>
    <secondary_id>NCI-2018-02667</secondary_id>
    <secondary_id>2018-0495</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <nct_id>NCT03752138</nct_id>
  </id_info>
  <brief_title>TK216 and Decitabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia</brief_title>
  <official_title>Phase I Study of TK216 in Patients With Relapsed and Refractory Leukemias</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of TK216 and decitabine when given&#xD;
      together in treating patients with acute myeloid leukemia that has come back or does not&#xD;
      respond to treatment. Drugs used in chemotherapy, such as TK216 and decitabine, work in&#xD;
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of&#xD;
      Ets-family transcription factor inhibitor TK216 (TK216) in patients with relapsed and&#xD;
      refractory (R/R) acute myeloid leukemia (AML). (Phase I Dose Escalation) II. To determine the&#xD;
      safety and tolerability of TK216 combined with decitabine in patients with relapsed and&#xD;
      refractory AML. (Combination Cohort)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Safety profile of TK216 as characterized by adverse event (AE) type, severity, timing and&#xD;
      relationship to study drug, as well as laboratory abnormalities in the first and subsequent&#xD;
      treatment cycles. (Phase I Dose Escalation) II. To explore the efficacy (complete remission&#xD;
      [CR], complete remission without platelet recovery [CRp], complete remission without blood&#xD;
      count recovery [CRi], or partial remission [PR]), of TK216 as a single-agent in patients with&#xD;
      R/R AML. (Phase I Dose Escalation) III. To assess overall survival (OS), and disease free&#xD;
      survival (DFS) in patients with R/R AML treated with TK216. (Phase I Dose Escalation) IV.&#xD;
      Duration of disease control defined as first date of disease control identified (either&#xD;
      CR/CRp/CRi, PR or SD) until the date of progression. (Phase I Dose Escalation) V. To explore&#xD;
      biomarkers of response and resistance in patients with R/R AML treated with TK216. (Phase I&#xD;
      Dose Escalation) VI. Safety profile of TK216 in combination with decitabine as characterized&#xD;
      by adverse event (AE) type, severity, timing and relationship to study drug, as well as&#xD;
      laboratory abnormalities in the first and subsequent treatment cycles. (Combination Cohort)&#xD;
      VII. To explore the efficacy (complete remission [CR], complete remission without platelet&#xD;
      recovery [CRp], complete remission without blood count recovery [CRi], or partial remission&#xD;
      [PR], of TK216 in combination with decitabine in patients with R/R AML. (Combination Cohort)&#xD;
      VIII. To assess overall survival (OS), and progression free survival (PFS) in patients with&#xD;
      R/R AML treated with TK216 + decitabine. (Combination Cohort) IX. Duration of disease control&#xD;
      defined as first date of disease control identified (either CR/CRp/CRi, PR or SD) until the&#xD;
      date of progression. (Combination Cohort) X. To explore biomarkers of response and resistance&#xD;
      in patients with R/R AML treated with TK216 + decitabine. (Combination Cohort)&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study.&#xD;
&#xD;
      Patients receive TK216 intravenously (IV) continuously on days 1-7 every 21 days, or&#xD;
      continuously on days 1-7 and 15-21 every 28 days. Patients also receive decitabine IV over 60&#xD;
      minutes on days 1-10 every 28 days. Treatment continues in the absence of disease progression&#xD;
      or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The supporting pharamceutical company elected not to pursue this study at this time.&#xD;
  </why_stopped>
  <start_date type="Anticipated">March 31, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Will be tabulated with frequency and percentage by grade, attribution to treatment, and by dose level/schedule.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Will be estimated alone with 95% confidence interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be estimated using the Kaplan-Meier method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be estimated using the Kaplan-Meier method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of disease control</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be estimated using the Kaplan-Meier method.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Recurrent Acute Myeloid Leukemia</condition>
  <condition>Refractory Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Group 1 Part 1 TK216: Days 1-7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive TK216 IV continuously on days 1-7 every 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 Part 1 TK216: Days 1-7 and 15-28</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive TK216 IV on days 1-7 and 15-21 every 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 TK216 + Decitabine 10mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive recommended dose of TK216 from Part 1 plus Decitabine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 TK216 + Decitabine 20 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive recommended dose of TK216 from Part 1 plus Decitabine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Phase: TK216 + Decitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients in the expansion cohort will receive the RP2D of TK216 and Decitabine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 1: TK216</intervention_name>
    <description>Starting Dose: 288 mg/m2 given by vein on Days 1-7 of a 21 day cycle.</description>
    <arm_group_label>Group 1 Part 1 TK216: Days 1-7</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 2: TK216</intervention_name>
    <description>Starting Dose: 144 mg/m2 given by vein on Days 1-7 and 15-21 of a 23 day cycle.</description>
    <arm_group_label>Group 2 Part 1 TK216: Days 1-7 and 15-28</arm_group_label>
    <other_name>TK-216</other_name>
    <other_name>TK216</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 2: Decitabine 10mg/m2</intervention_name>
    <description>10mg/m2 by vein on Days 1-10 of a 28 day cycle.</description>
    <arm_group_label>Part 2 TK216 + Decitabine 10mg/m2</arm_group_label>
    <other_name>Dacogen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 2: Decitabine 20 mg/m2</intervention_name>
    <description>20 mg/m2 by vein on Days 1-10 of a 28 dayi cycle.</description>
    <arm_group_label>Part 2 TK216 + Decitabine 20 mg/m2</arm_group_label>
    <other_name>Dacogen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Expansion Phase TK216</intervention_name>
    <description>Expansion cohort will receive the RP2D of TK216</description>
    <arm_group_label>Expansion Phase: TK216 + Decitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Expansion Phase Decitabine</intervention_name>
    <description>Expansion cohort will receive the RP2D of Decitabine</description>
    <arm_group_label>Expansion Phase: TK216 + Decitabine</arm_group_label>
    <other_name>Dacogen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 2: TK216</intervention_name>
    <description>Recommended dose from Part 1.</description>
    <arm_group_label>Part 2 TK216 + Decitabine 10mg/m2</arm_group_label>
    <arm_group_label>Part 2 TK216 + Decitabine 20 mg/m2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R)&#xD;
             acute myeloid leukemia for which no available standard therapies are indicated or&#xD;
             anticipated to result in a durable response&#xD;
&#xD;
          -  Patients must not have had leukemia therapy for 14 days prior to starting TK216.&#xD;
             However, patients with rapidly proliferative disease may receive hydroxyurea as needed&#xD;
             until 24 hours prior to starting therapy on this protocol and during the first cycle&#xD;
             of study&#xD;
&#xD;
          -  Bilirubin =&lt; 2 mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =&lt; 3 x upper&#xD;
             limit of normal (ULN) -- or =&lt; 5 x ULN if related to leukemic involvement&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Known cardiac ejection fraction of &gt; or = 45% within the past 3 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 2&#xD;
&#xD;
          -  A negative urine pregnancy test is required within 1 week for all women of&#xD;
             childbearing potential prior to enrolling on this trial&#xD;
&#xD;
          -  Patient must have the ability to understand the requirements of the study and signed&#xD;
             informed consent. A signed informed consent by the patient or his legally authorized&#xD;
             representative is required prior to their enrollment on the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women are excluded from this study because the agent used in this study has&#xD;
             the potential for teratogenic or abortifacient effects. Because there is a potential&#xD;
             risk for adverse events in nursing infants secondary to treatment of the mother with&#xD;
             the chemotherapy agents, breastfeeding should also be avoided&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to active uncontrolled&#xD;
             infection, symptomatic congestive heart failure (New York Heart Association [NYHA]&#xD;
             class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia,&#xD;
             or psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  Patient with documented hypersensitivity to any of the components of the therapy&#xD;
             program&#xD;
&#xD;
          -  Patients with active, uncontrolled central nervous system (CNS) leukemia will not be&#xD;
             eligible&#xD;
&#xD;
          -  Men and women of childbearing potential who do not practice contraception. Women of&#xD;
             childbearing potential and men must agree to use at least 1 form of barrier birth&#xD;
             control (such as condom) prior to study entry and for the duration of study&#xD;
             participation&#xD;
&#xD;
          -  Patients with known history of serous retinopathy will not be eligible&#xD;
&#xD;
          -  Prior treatment with TK216&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tapan Kadia</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>May 2, 2019</last_update_submitted>
  <last_update_submitted_qc>May 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Decitabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03752138
org study id: 2018-0495
secondary id: NCI-2018-02667
secondary id: 2018-0495
secondary id: P30CA016672
nct id: NCT03752138
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: Up to 30 days
description: Will be tabulated with frequency and percentage by grade, attribution to treatment, and by dose level/schedule.
measure: Response rate
time frame: Up to 30 days
description: Will be estimated alone with 95% confidence interval.
measure: Overall survival
time frame: Up to 1 year
description: Will be estimated using the Kaplan-Meier method.
measure: Disease free survival
time frame: Up to 1 year
description: Will be estimated using the Kaplan-Meier method.
measure: Duration of disease control
time frame: Up to 1 year
description: Will be estimated using the Kaplan-Meier method.
arm group label: Group 1 Part 1 TK216: Days 1-7
arm group type: Experimental
description: Patients receive TK216 IV continuously on days 1-7 every 21 days.
arm group label: Group 2 Part 1 TK216: Days 1-7 and 15-28
arm group type: Experimental
description: Patients receive TK216 IV on days 1-7 and 15-21 every 28 days.
arm group label: Part 2 TK216 + Decitabine 10mg/m2
arm group type: Experimental
description: Patients receive recommended dose of TK216 from Part 1 plus Decitabine.
arm group label: Part 2 TK216 + Decitabine 20 mg/m2
arm group type: Experimental
description: Patients receive recommended dose of TK216 from Part 1 plus Decitabine.
arm group label: Expansion Phase: TK216 + Decitabine
arm group type: Experimental
description: All patients in the expansion cohort will receive the RP2D of TK216 and Decitabine.
intervention type: Drug
intervention name: Group 1: TK216
description: Starting Dose: 288 mg/m2 given by vein on Days 1-7 of a 21 day cycle.
arm group label: Group 1 Part 1 TK216: Days 1-7
intervention type: Drug
intervention name: Group 2: TK216
description: Starting Dose: 144 mg/m2 given by vein on Days 1-7 and 15-21 of a 23 day cycle.
arm group label: Group 2 Part 1 TK216: Days 1-7 and 15-28
other name: TK-216
other name: TK216
intervention type: Drug
intervention name: Part 2: Decitabine 10mg/m2
description: 10mg/m2 by vein on Days 1-10 of a 28 day cycle.
arm group label: Part 2 TK216 + Decitabine 10mg/m2
other name: Dacogen
intervention type: Drug
intervention name: Part 2: Decitabine 20 mg/m2
description: 20 mg/m2 by vein on Days 1-10 of a 28 dayi cycle.
arm group label: Part 2 TK216 + Decitabine 20 mg/m2
other name: Dacogen
intervention type: Drug
intervention name: Expansion Phase TK216
description: Expansion cohort will receive the RP2D of TK216
arm group label: Expansion Phase: TK216 + Decitabine
intervention type: Drug
intervention name: Expansion Phase Decitabine
description: Expansion cohort will receive the RP2D of Decitabine
arm group label: Expansion Phase: TK216 + Decitabine
other name: Dacogen
intervention type: Drug
intervention name: Part 2: TK216
description: Recommended dose from Part 1.
arm group label: Part 2 TK216 + Decitabine 10mg/m2
arm group label: Part 2 TK216 + Decitabine 20 mg/m2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tapan Kadia
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Decitabine