<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/NCT01681537</url>
  </required_header>
  <id_info>
    <org_study_id>12-202</org_study_id>
    <nct_id>NCT01681537</nct_id>
  </id_info>
  <brief_title>Lenalidomide Plus Chemotherapy for AML</brief_title>
  <official_title>A Phase I Study of Lenalidomide Plus Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine for the Reinduction of Patients With Acute Myelogenous Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is a Phase I clinical trial. Phase I clinical trials test the safety of&#xD;
      an investigational combination of drugs. Phase I studies also try to define the appropriate&#xD;
      dose of the investigational combination of drugs to use for further studies.&#xD;
      &quot;Investigational&quot; means that the combination of drugs is still being studied and that&#xD;
      research doctors are trying to find out more about it. It also means that the FDA has not&#xD;
      approved this combination of drugs for AML. As part of this research study, you will take&#xD;
      lenalidomide in combination with MEC. MEC are FDA approved chemotherapy drugs that are&#xD;
      commonly used in the treatment of AML. Lenalidomide is approved by the FDA for patients with&#xD;
      multiple myeloma, and some patients with myelodysplasia. Lenalidomide is considered&#xD;
      investigational in this research study because it is not approved by the FDA for patients&#xD;
      with AML.&#xD;
&#xD;
      Lenalidomide is a drug that affects the immune system, called an immunomodulatory drug or&#xD;
      IMID. This drug is successful in the treatment of patients with multiple myeloma and some&#xD;
      patients with myelodysplasia, a pre-leukemic condition. Other research studies suggest that&#xD;
      lenalidomide may also be effective in patients with AML. Since we know that many patients who&#xD;
      receive MEC chemotherapy alone do not have a prolonged remission (time free from leukemia),&#xD;
      we are studying the addition of lenalidomide to MEC.&#xD;
&#xD;
      In this research study, we are looking for the highest dose of lenalidomide that can be given&#xD;
      safely with MEC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After undergoing screening procedures to confirm that you are eligible to participate in the&#xD;
      research study you will be admitted to the hospital. You will likely receive the majority of&#xD;
      treatment on an inpatient basis. You will remain in the hospital for at least Days 4-8 and&#xD;
      will be discharged at the discretion of your study doctor. It is likely that you will be&#xD;
      hospitalized for several weeks due to the risk of infection after chemotherapy.&#xD;
&#xD;
      Since we are looking for the highest dose of the study drug that can be administered safely&#xD;
      without severe or unmanageable side effects in participants that have relapsed or refractory&#xD;
      AML, not everyone who participates in this research study will receive the same dose of the&#xD;
      study drug. The dose you get will depend on the number of participants who have been enrolled&#xD;
      in the study before you and how well they have tolerated their doses.&#xD;
&#xD;
      If you take part in this study you will be given a study drug-dosing calendar. There is only&#xD;
      one cycle of treatment, which will be 28 days long. On Days 1 to 14 you will receive the&#xD;
      lenalidomide orally. On Days 4-8 you will receive MEC chemotherapy: mitoxantrone by IV&#xD;
      (intravenously, into your vein) over 30 minutes, etoposide by IV over one hour, and&#xD;
      cytarabine by IV over one hour.&#xD;
&#xD;
      While on this study you will undergo a daily clinical exam for the first 14 days and then at&#xD;
      least twice a week until your blood counts recover from treatment. A clinical exam consists&#xD;
      of a physical exam, questions about your general health and specific questions about any&#xD;
      problems that you might be having and any medications you may be taking. You will also&#xD;
      undergo blood tests to assess your disease status and determine organ function level. This&#xD;
      will happen daily for the first 14 days and then at least once a week (but up to 3 times per&#xD;
      week) until your blood counts recover from treatment. Additionally a bone marrow&#xD;
      aspirate/biopsy will be completed at the time of blood cell count recovery (usually between&#xD;
      days 20 and 45) and as clinically indicated.&#xD;
&#xD;
      We would like to keep track of your medical condition for up to two years after your final&#xD;
      dose of study drug. We would like to do this by getting in touch with you every 6 months to&#xD;
      see how you are doing. Keeping in touch with you and checking your condition helps us look at&#xD;
      the long-term effects fo the research study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of lenalidomide plus conventional chemotherapy for relapsed AML</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluation of the safety of lenalidomide in combination with conventional chemotherapy for relapsed acute myelogenous leukemia. Dose limiting toxicity is defined as a Grade IV rash or delayed neutrophil or platelet recovery beyond Day 45 after start of chemotherapy in the absence of disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Days to neutrophil recovery</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluation of neutrophil recovery (the first 3 days of ANC&gt;500)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Remission Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluation of the complete remission rate and the complete remission rate without platelet recovery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related mortality</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluation of the treatment-related mortality, the number of non-relapse related deaths in the first 45 days of starting treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusion Support</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluation of transfusion support, the number of red blood cell and platelet transfusions needed in the first 45 days of treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Acute Myelogenous Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide and re-induction chemotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitoxantrone</intervention_name>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary refractory disease following at least one cycle of induction therapy or first&#xD;
             relapse or higher&#xD;
&#xD;
          -  Must be registered into RevAssist program&#xD;
&#xD;
          -  Able and willing to adhere to study schedule and other protocol requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Known hypersensitivity to thalidomide or lenalidomide&#xD;
&#xD;
          -  Known seropositive for HIV&#xD;
&#xD;
          -  Have had myocardial infarction within 6 months of enrollment or NYHA Class III or IV&#xD;
             heart failure&#xD;
&#xD;
          -  Other serious medical conditions or psychiatric conditions&#xD;
&#xD;
          -  Major surgery within 28 days prior to treatment&#xD;
&#xD;
          -  Received investigational agent or cytotoxic chemotherapy (except hydroxyurea) within 2&#xD;
             weeks of study&#xD;
&#xD;
          -  Acute promyelocytic leukemia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karen Ballen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>September 2, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>March 15, 2016</last_update_submitted>
  <last_update_submitted_qc>March 15, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 17, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Karen Ballen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Relapsed</keyword>
  <keyword>Refractory</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>Cytarabine</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Mitoxantrone</mesh_term>
    <mesh_term>Lenalidomide</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/NCT01681537
org study id: 12-202
nct id: NCT01681537
lead sponsor: 
has dmc: Yes
This research study is a Phase I clinical trial. Phase I clinical trials test the safety of
      an investigational combination of drugs. Phase I studies also try to define the appropriate
      dose of the investigational combination of drugs to use for further studies.
      "Investigational" means that the combination of drugs is still being studied and that
      research doctors are trying to find out more about it. It also means that the FDA has not
      approved this combination of drugs for AML. As part of this research study, you will take
      lenalidomide in combination with MEC. MEC are FDA approved chemotherapy drugs that are
      commonly used in the treatment of AML. Lenalidomide is approved by the FDA for patients with
      multiple myeloma, and some patients with myelodysplasia. Lenalidomide is considered
      investigational in this research study because it is not approved by the FDA for patients
      with AML.

      Lenalidomide is a drug that affects the immune system, called an immunomodulatory drug or
      IMID. This drug is successful in the treatment of patients with multiple myeloma and some
      patients with myelodysplasia, a pre-leukemic condition. Other research studies suggest that
      lenalidomide may also be effective in patients with AML. Since we know that many patients who
      receive MEC chemotherapy alone do not have a prolonged remission (time free from leukemia),
      we are studying the addition of lenalidomide to MEC.

      In this research study, we are looking for the highest dose of lenalidomide that can be given
      safely with MEC.
After undergoing screening procedures to confirm that you are eligible to participate in the
      research study you will be admitted to the hospital. You will likely receive the majority of
      treatment on an inpatient basis. You will remain in the hospital for at least Days 4-8 and
      will be discharged at the discretion of your study doctor. It is likely that you will be
      hospitalized for several weeks due to the risk of infection after chemotherapy.

      Since we are looking for the highest dose of the study drug that can be administered safely
      without severe or unmanageable side effects in participants that have relapsed or refractory
      AML, not everyone who participates in this research study will receive the same dose of the
      study drug. The dose you get will depend on the number of participants who have been enrolled
      in the study before you and how well they have tolerated their doses.

      If you take part in this study you will be given a study drug-dosing calendar. There is only
      one cycle of treatment, which will be 28 days long. On Days 1 to 14 you will receive the
      lenalidomide orally. On Days 4-8 you will receive MEC chemotherapy: mitoxantrone by IV
      (intravenously, into your vein) over 30 minutes, etoposide by IV over one hour, and
      cytarabine by IV over one hour.

      While on this study you will undergo a daily clinical exam for the first 14 days and then at
      least twice a week until your blood counts recover from treatment. A clinical exam consists
      of a physical exam, questions about your general health and specific questions about any
      problems that you might be having and any medications you may be taking. You will also
      undergo blood tests to assess your disease status and determine organ function level. This
      will happen daily for the first 14 days and then at least once a week (but up to 3 times per
      week) until your blood counts recover from treatment. Additionally a bone marrow
      aspirate/biopsy will be completed at the time of blood cell count recovery (usually between
      days 20 and 45) and as clinically indicated.

      We would like to keep track of your medical condition for up to two years after your final
      dose of study drug. We would like to do this by getting in touch with you every 6 months to
      see how you are doing. Keeping in touch with you and checking your condition helps us look at
      the long-term effects fo the research study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of lenalidomide plus conventional chemotherapy for relapsed AML
time frame: 2 years
description: Evaluation of the safety of lenalidomide in combination with conventional chemotherapy for relapsed acute myelogenous leukemia. Dose limiting toxicity is defined as a Grade IV rash or delayed neutrophil or platelet recovery beyond Day 45 after start of chemotherapy in the absence of disease
measure: Days to neutrophil recovery
time frame: 2 years
description: Evaluation of neutrophil recovery (the first 3 days of ANC>500)
measure: Complete Remission Rate
time frame: 2 years
description: Evaluation of the complete remission rate and the complete remission rate without platelet recovery
measure: Treatment-related mortality
time frame: 2 years
description: Evaluation of the treatment-related mortality, the number of non-relapse related deaths in the first 45 days of starting treatment
measure: Transfusion Support
time frame: 2 years
description: Evaluation of transfusion support, the number of red blood cell and platelet transfusions needed in the first 45 days of treatment
arm group label: Treatment Arm
arm group type: Experimental
description: Lenalidomide and re-induction chemotherapy
intervention type: Drug
intervention name: Lenalidomide
arm group label: Treatment Arm
intervention type: Drug
intervention name: Mitoxantrone
arm group label: Treatment Arm
intervention type: Drug
intervention name: Etoposide
arm group label: Treatment Arm
intervention type: Drug
intervention name: Cytarabine
arm group label: Treatment Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Karen Ballen, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Karen Ballen
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Etoposide
mesh term: Mitoxantrone
mesh term: Lenalidomide