<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/NCT03839446</url>
  </required_header>
  <id_info>
    <org_study_id>HCC 18-111</org_study_id>
    <nct_id>NCT03839446</nct_id>
  </id_info>
  <brief_title>Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy</brief_title>
  <official_title>Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Robert Redner, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</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 study is an open-label, single arm phase II study which will examine the efficacy and&#xD;
      toxicity of the combination therapy of GO, mitoxantrone and etoposide in patients who did not&#xD;
      respond to first line induction therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be treated inpatient. Patients will receive mitoxantrone 10mg/m2&#xD;
      administered intravenous piggyback (IVPB) in 50ml 0.9% normal saline over 15 minutes on days&#xD;
      1-5 and etoposide 100 mg/m2 administered intravenously in 500 ml of 0.9% sodium chloride over&#xD;
      2 hours on days 1-5.&#xD;
&#xD;
      On day 6, patients will receive a single dose of GO 3mg/m2 (maximum dose 4.5mg). Patients&#xD;
      will be pre-medicated 1 hour prior to the GO infusion with diphenhydramine 50mg administered&#xD;
      orally or intravenously, acetaminophen 650 mg administered orally or intravenously and 1mg/kg&#xD;
      methylprednisolone or an equivalent dose of alternative corticosteroid administered IV within&#xD;
      30 minutes prior to infusion of GO. GO will be administered intravenously in 50 ml (or other&#xD;
      suitable volume resulting in a final GO concentration between 0.075 mg/mL to 0.234 mg/mL) of&#xD;
      0.9% sodium chloride over 2 hours. Doses of GO will be based on BSA calculated using actual&#xD;
      body weight with a cap of 4.5mg. Vital signs will be recorded within one hour prior to the&#xD;
      infusion and then every 30 minutes during the infusion and 30 minutes and one hour after&#xD;
      completion of infusion. An additional dose of methylprednisolone 1 mg/kg IV may be given for&#xD;
      any sign of infusion reaction, such as fever, chills, hypotension, or dyspnea occurring&#xD;
      during the GO infusion or within 4 hours after the GO infusion.&#xD;
&#xD;
      For dose modifications based on kidney and liver function please see the treatment schema at&#xD;
      the end of the study.&#xD;
&#xD;
      Supportive care including blood product transfusions, antiemetic medications, antiviral and&#xD;
      antifungal medications, growth factor support, tumor lysis syndrome prophylaxis, or empiric&#xD;
      antibiotics may be used at the clinical discretion of the provider.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 28, 2019</start_date>
  <completion_date type="Actual">February 2, 2023</completion_date>
  <primary_completion_date type="Actual">January 11, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open label single arm</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete Remission Rate</measure>
    <time_frame>Up to six weeks</time_frame>
    <description>The number of patients that experience complete remission / total number of patients.&#xD;
Complete Remission in AML is defined as:&#xD;
1. Normal values for absolute neutrophil count (&gt;1000/microL) and platelet count (&gt;100,000/microL), and independence from red cell transfusion. 2. A bone marrow biopsy that reveals no clusters or collections of blast cells. Extramedullary leukemia (eg, central nervous system or soft tissue involvement) must be absent. 3. A bone marrow aspiration that reveals normal maturation of all cellular components (ie, erythrocytic, granulocytic, and megakaryocytic series). No requirement for bone marrow cellularity. 4. &lt; 5 percent blast cells are present in the bone marrow, and none can have a leukemic phenotype (eg, Auer rods). 5. The absence of a previously detected clonal cytogenetic abnormality (ie, complete cytogenetic remission, CRc) confirms the morphologic diagnosis of CR but is not currently a required criterion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Up to five years</time_frame>
    <description>The length of time during and after the treatment that a patient lives with Acute Myeloid Leukemia that does not get worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to five years</time_frame>
    <description>The length of time from the start of treatment that patients are still alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytogenetic Status</measure>
    <time_frame>1 day (Determine once, at the time of AML diagnosis)</time_frame>
    <description>Poor, Intermediate, Favorable chromosomal status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of blasts</measure>
    <time_frame>1 day (Determined once, after treatment)</time_frame>
    <description>Percent of blasts present in the bone marrow after therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>mitoxantrone + etoposide + gemtuzumab ozogamicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mitoxantrone + etoposide + gemtuzumab ozogamicin</intervention_name>
    <description>10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6.</description>
    <arm_group_label>mitoxantrone + etoposide + gemtuzumab ozogamicin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to understand and have the ability to provide written consent.&#xD;
&#xD;
          2. Age: ≥18 and ≤75 years-old&#xD;
&#xD;
          3. Patients with newly diagnosed AML based on the World Health Organization&#xD;
             classification who have persistent disease after their first course treatment with an&#xD;
             anthracycline and cytarabine (the diagnosis of persistent disease, which is defined as&#xD;
             ≥10% blasts by morphology for this trial or &gt;5% blasts if they have had an increase in&#xD;
             blasts from the last bone marrow biopsy, will be based on their assessment after bone&#xD;
             marrow aspiration and/or biopsy after initial treatment).&#xD;
&#xD;
          4. Patients with myelodysplastic syndrome (MDS) based on the World Health Organization&#xD;
             classification who have persistent disease after their treatment with an anthracycline&#xD;
             and cytarabine (the diagnosis of persistent disease, which is defined as ≥10% blasts&#xD;
             by morphology for this trial or &gt;5% blasts if they have had an increase in blasts from&#xD;
             the last bone marrow biopsy, will be based on their assessment after bone marrow&#xD;
             aspiration and/or biopsy after initial treatment).&#xD;
&#xD;
          5. CD33 expression in ≥ 30% of leukemic blasts on the bone marrow.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix I).&#xD;
&#xD;
          7. Patients must have the following laboratory values prior to beginning protocol&#xD;
             treatment:&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 30 mL/min (using the Cockcroft-Gault equation&#xD;
                  CL creatinine = ((140-age) x body mass X 0.85 if female)/72 x creatinine where&#xD;
                  age is given in years, body mass is given in Kg and creatinine is given in&#xD;
                  mg/dl).&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) ≤ 2.5 x upper normal limit.&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit.&#xD;
&#xD;
               -  Total bilirubin ≤ 2 x upper normal limit. Note: As many eligible patients will be&#xD;
                  pancytopenic secondary to their disease or prior treatments, hematologic&#xD;
                  abnormalities will not be used as criteria for entry or exclusion.&#xD;
&#xD;
          8. Left ventricular ejection fraction (LVEF) ≥50 %.&#xD;
&#xD;
          9. Females of child-bearing potential must have a negative pregnancy test during&#xD;
             screening and all subjects must agree to use an effective method of contraception. A&#xD;
             woman is eligible to enter and participate in the study if she is of:&#xD;
&#xD;
               1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant)&#xD;
                  including any female who has had a hysterectomy or has had a bilateral&#xD;
                  oophorectomy (ovariectomy).&#xD;
&#xD;
               2. Childbearing potential, has a negative serum pregnancy test during the screening&#xD;
                  period and agrees to avoid sexual activity or use contraception from screening&#xD;
                  through follow-up (method of birth control if the patient is not neutropenic&#xD;
                  include the use of a diaphragm, intrauterine device, contraceptive sponge and/or&#xD;
                  usage of male condom with a spermicide from the partner). A man with a female&#xD;
                  partner of childbearing potential is eligible to enter and participate in the&#xD;
                  study if he has either had a prior vasectomy or agrees to avoid sexual activity&#xD;
                  or use adequate contraception (as described above) from screening through&#xD;
                  follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the&#xD;
             World Health Organization.&#xD;
&#xD;
          2. Relapsed acute leukemia.&#xD;
&#xD;
          3. Bi-lineage or bi-phenotypic leukemia.&#xD;
&#xD;
          4. Prior use of mitoxantrone or etoposide or GO.&#xD;
&#xD;
          5. Previous allogeneic hematopoietic cell transplantation.&#xD;
&#xD;
          6. First induction course of acute myeloid leukemia with CPX-351.&#xD;
&#xD;
          7. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of treating investigator.&#xD;
&#xD;
          8. Has known history of active Hepatitis B (HBsAg reactive) or Hepatitis C (detectable&#xD;
             HCV RNA).&#xD;
&#xD;
          9. Uncontrolled, life-threatening infection that is not responding to antimicrobial&#xD;
             therapy.&#xD;
&#xD;
         10. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         11. Patient may have not received any other investigational anti-neoplastic agents within&#xD;
             4 weeks from the start of therapy.&#xD;
&#xD;
         12. Concurrent active malignancy; exceptions include patients who have been disease free&#xD;
             for 5 years, patients with a history of completely resected non-melanoma skin cancer&#xD;
             or successfully treated in situ carcinoma, or patients with another malignancy with&#xD;
             better prognosis than AML.&#xD;
&#xD;
         13. Women who are pregnant or breastfeeding.&#xD;
&#xD;
         14. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated&#xD;
             respiratory or cardiac disease).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Redner Robert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UPMC Hillman Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Robert Redner, MD</investigator_full_name>
    <investigator_title>Professor of Medicine - Hematology/Oncology</investigator_title>
  </responsible_party>
  <keyword>cytogenetic status</keyword>
  <keyword>mitoxantrone</keyword>
  <keyword>etoposide</keyword>
  <keyword>gemtuzumab ozogamicin</keyword>
  <keyword>bone marrow</keyword>
  <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>Etoposide</mesh_term>
    <mesh_term>Mitoxantrone</mesh_term>
    <mesh_term>Gemtuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03839446
org study id: HCC 18-111
nct id: NCT03839446
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is an open-label, single arm phase II study which will examine the efficacy and
      toxicity of the combination therapy of GO, mitoxantrone and etoposide in patients who did not
      respond to first line induction therapy.
Eligible patients will be treated inpatient. Patients will receive mitoxantrone 10mg/m2
      administered intravenous piggyback (IVPB) in 50ml 0.9% normal saline over 15 minutes on days
      1-5 and etoposide 100 mg/m2 administered intravenously in 500 ml of 0.9% sodium chloride over
      2 hours on days 1-5.

      On day 6, patients will receive a single dose of GO 3mg/m2 (maximum dose 4.5mg). Patients
      will be pre-medicated 1 hour prior to the GO infusion with diphenhydramine 50mg administered
      orally or intravenously, acetaminophen 650 mg administered orally or intravenously and 1mg/kg
      methylprednisolone or an equivalent dose of alternative corticosteroid administered IV within
      30 minutes prior to infusion of GO. GO will be administered intravenously in 50 ml (or other
      suitable volume resulting in a final GO concentration between 0.075 mg/mL to 0.234 mg/mL) of
      0.9% sodium chloride over 2 hours. Doses of GO will be based on BSA calculated using actual
      body weight with a cap of 4.5mg. Vital signs will be recorded within one hour prior to the
      infusion and then every 30 minutes during the infusion and 30 minutes and one hour after
      completion of infusion. An additional dose of methylprednisolone 1 mg/kg IV may be given for
      any sign of infusion reaction, such as fever, chills, hypotension, or dyspnea occurring
      during the GO infusion or within 4 hours after the GO infusion.

      For dose modifications based on kidney and liver function please see the treatment schema at
      the end of the study.

      Supportive care including blood product transfusions, antiemetic medications, antiviral and
      antifungal medications, growth factor support, tumor lysis syndrome prophylaxis, or empiric
      antibiotics may be used at the clinical discretion of the provider.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open label single arm
primary purpose: Treatment
masking: None (Open Label)
measure: Complete Remission Rate
time frame: Up to six weeks
description: The number of patients that experience complete remission / total number of patients.
Complete Remission in AML is defined as:
1. Normal values for absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL), and independence from red cell transfusion. 2. A bone marrow biopsy that reveals no clusters or collections of blast cells. Extramedullary leukemia (eg, central nervous system or soft tissue involvement) must be absent. 3. A bone marrow aspiration that reveals normal maturation of all cellular components (ie, erythrocytic, granulocytic, and megakaryocytic series). No requirement for bone marrow cellularity. 4. < 5 percent blast cells are present in the bone marrow, and none can have a leukemic phenotype (eg, Auer rods). 5. The absence of a previously detected clonal cytogenetic abnormality (ie, complete cytogenetic remission, CRc) confirms the morphologic diagnosis of CR but is not currently a required criterion.
measure: Progression-free Survival (PFS)
time frame: Up to five years
description: The length of time during and after the treatment that a patient lives with Acute Myeloid Leukemia that does not get worse.
measure: Overall Survival (OS)
time frame: Up to five years
description: The length of time from the start of treatment that patients are still alive.
measure: Cytogenetic Status
time frame: 1 day (Determine once, at the time of AML diagnosis)
description: Poor, Intermediate, Favorable chromosomal status.
measure: Percent of blasts
time frame: 1 day (Determined once, after treatment)
description: Percent of blasts present in the bone marrow after therapy.
arm group label: mitoxantrone + etoposide + gemtuzumab ozogamicin
arm group type: Experimental
description: 10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6
intervention type: Drug
intervention name: mitoxantrone + etoposide + gemtuzumab ozogamicin
description: 10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6.
arm group label: mitoxantrone + etoposide + gemtuzumab ozogamicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Redner Robert, MD
role: Principal Investigator
affiliation: UPMC Hillman Cancer Center
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Robert Redner, MD
investigator title: Professor of Medicine - Hematology/Oncology
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Etoposide
mesh term: Mitoxantrone
mesh term: Gemtuzumab
sharing ipd: No