<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/NCT02255162</url>
  </required_header>
  <id_info>
    <org_study_id>14-265</org_study_id>
    <nct_id>NCT02255162</nct_id>
  </id_info>
  <brief_title>Lenalidomide in Combination With Microtransplantation as Post-remission Therapy in AML</brief_title>
  <official_title>Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is evaluating the safety and tolerability of the drug lenalidomide in&#xD;
      combination with and following mismatched related donor microtransplantation in high risk AML&#xD;
      patients in first remission. This study also aims to define the maximum tolerated dose (MTD)&#xD;
      of lenalidomide given in this setting.&#xD;
&#xD;
      Microtransplantation seeks to give the participant donor cells in hopes that those cells can&#xD;
      attack the underlying cancer. However, since the donor cells do not replace all of the host&#xD;
      cells, it can hopefully avoid many of the serious risks involved with standard transplant,&#xD;
      including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the&#xD;
      participant's normal body. Recent studies have suggested that lenalidomide can help aid donor&#xD;
      cells to attack cancer when given after a stem cell transplant. This trial is trying to see&#xD;
      if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part&#xD;
      of microtransplantation.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been&#xD;
      approved for other uses such as in the treatment of other cancers including multiple myeloma&#xD;
      and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has&#xD;
      not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the&#xD;
      Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact&#xD;
      antitumor mechanism of action of lenalidomide is unknown.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After the screening procedures confirm that the participant is eligible to participate in the&#xD;
      research study. The participant will be given a study drug-dosing calendar.&#xD;
&#xD;
      The investigators are looking for the highest dose of the study drug that can be administered&#xD;
      safely without severe or unmanageable side effects in participants, not everyone who&#xD;
      participates in this research study will receive the same dose of the study drug. The dose&#xD;
      given will depend on the number of participants who have been enrolled in the study prior and&#xD;
      how well they have tolerated their doses. Participants will receive the following:&#xD;
&#xD;
        -  Cytarabine&#xD;
&#xD;
        -  Microtransplantation&#xD;
&#xD;
        -  Lenalidomide&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation</measure>
    <time_frame>Baseline, 42 Days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1 Year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess immunomodulatory effects of this combination through measurement of T cell subsets by flow cytometric techniques and through microchimerism analysis at multiple points on study</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To identify incidence and severity of acute and chronic graft versus host disease (GVHD).</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To detect and categorize, according to severity, the cumulative incidences of toxicities</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <condition>Acute Myelocytic Leukemia</condition>
  <condition>Acute Myelogenous Leukemia</condition>
  <condition>Acute Granulocytic Leukemia</condition>
  <condition>Acute Non-Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.&#xD;
Participants will receive the following:&#xD;
Cytarabine-intravenous, fixed dosage, given 5 times during cycle&#xD;
HLA-mismatched stem-cell microtransplantation&#xD;
Lenalidomide-administered daily per cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Patients will receive lenalidomide starting on day 6 of each post-remission cycle, following conclusion of cytarabine post-remission therapy on days 1-5. Following count recovery in the third post-remission cycle, patients will then receive lenalidomide daily as a maintenance therapy.</description>
    <arm_group_label>Lenalidomide</arm_group_label>
    <other_name>•Revlimid®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>HLA-mismatched stem-cell Microtransplantation</intervention_name>
    <description>Patient will receive HLA-mismatched stem cell microtransplant infusion on day 6 of each post-remission cycle, following conclusion of course of cytarabine in each cycle.</description>
    <arm_group_label>Lenalidomide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Patients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle.</description>
    <arm_group_label>Lenalidomide</arm_group_label>
    <other_name>Cytosar-U ®</other_name>
    <other_name>1-β-Arabinofuranosylcytosine</other_name>
    <other_name>Arabinosylcytosine</other_name>
    <other_name>Cytosine arabinoside</other_name>
    <other_name>Ara-C</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Recipient Inclusion Criteria&#xD;
&#xD;
          -  Adults, aged 18 through 75 years of age, with pathologically confirmed acute&#xD;
             myelogenous leukemia, in pathologically confirmed complete remission following&#xD;
             anti-leukemic therapy.&#xD;
&#xD;
          -  AST, ALT and Alkaline Phosphatase &lt;5x Upper Limit normal (ULN), direct bilirubin &lt; 2.0&#xD;
             mg/dl.&#xD;
&#xD;
          -  Adequate renal function as defined by: calculated creatinine clearance ≥ 60 mL/min&#xD;
             (Cockcroft-Gault Formula) or serum Cr less than institution ULN (the elderly will&#xD;
             often have &lt; 60 GFR)&#xD;
&#xD;
          -  ECOG performance status 0-2.&#xD;
&#xD;
          -  Have a diagnosis of high-risk AML as established by a poor-risk karyotype, adverse&#xD;
             risk by ELN criteria, a therapy-related AML, age ≥ 60 or with antecedent hematologic&#xD;
             disorder&#xD;
&#xD;
          -  LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram&#xD;
&#xD;
          -  Patients, or appropriate designee, must be able to provide informed consent.&#xD;
&#xD;
          -  Must not have received systemic anti-neoplastic therapy, including radiotherapy within&#xD;
             14 days of study treatment.&#xD;
&#xD;
          -  Female patients of childbearing age must have negative pregnancy test.&#xD;
&#xD;
          -  Male subject agrees to use an acceptable method for contraception during the entire&#xD;
             study treatment period and through 6 months after the last dose of lenalidomide.&#xD;
&#xD;
          -  All study participants must be registered into the mandatory Revlimid REMS® program,&#xD;
             and be willing and able to comply with the requirements of the REMS® program.&#xD;
&#xD;
          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as&#xD;
             required in the Revlimid REMS® program. If needed, patients should be able to take&#xD;
             aspirin (81 or 325 mg) daily as prophylactic anticoagulation.&#xD;
&#xD;
          -  Donor Inclusion Criteria&#xD;
&#xD;
          -  Haploidentical 1st-degree relative as defined by 3/6 or 4/6 HLA-matched at HLA -A, -B,&#xD;
             or -DRB1 who is 18-70 years of age&#xD;
&#xD;
          -  ECOG performance status 0 or 1&#xD;
&#xD;
          -  Excellent health per conventional pre-donor history (medical and psychosocial&#xD;
             evaluation)&#xD;
&#xD;
          -  No positive testing for viral infection (HbsAg, HIV, HCV)&#xD;
&#xD;
          -  Donor ability to understand and provide informed consent&#xD;
&#xD;
          -  Meets standard institutional criteria for GCSF mobilized PBSC donation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recipient Exclusion Criteria&#xD;
&#xD;
          -  Diagnosis of acute promyelocytic leukemia&#xD;
&#xD;
          -  Active refractory or relapsed acute leukemia&#xD;
&#xD;
          -  Prior use of fludarabine, as this agent has been associated with higher subsequent&#xD;
             rates of graft versus host disease&#xD;
&#xD;
          -  Individuals with a history of a different malignancy are ineligible except for the&#xD;
             following circumstances. Individuals with a history of other malignancies are eligible&#xD;
             if they have been disease-free for at least 3 years and are deemed by the investigator&#xD;
             to be at low risk for recurrence of that malignancy. Individuals with the following&#xD;
             cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer&#xD;
             in situ, and basal cell or squamous cell carcinoma of the skin.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness that would limit compliance with study requirements.&#xD;
&#xD;
          -  HIV-positive individuals on combination antiretroviral therapy are ineligible because&#xD;
             of the potential for pharmacokinetic interactions with study drug. In addition, these&#xD;
             individuals are at increased risk of lethal infections when treated with&#xD;
             marrow-suppressive therapy.&#xD;
&#xD;
          -  A diagnosis of active hepatitis B or C as defined by detectable viral load assays in&#xD;
             the blood&#xD;
&#xD;
          -  Known hypersensitivity to thalidomide or lenalidomide.&#xD;
&#xD;
          -  The development of erythema nodosum if characterized by a desquamating rash while&#xD;
             taking lenalidomide.&#xD;
&#xD;
          -  Significant cardiac disease as determined by the investigator including:&#xD;
&#xD;
               -  Known or suspected cardiac amyloidosis&#xD;
&#xD;
               -  Congestive heart failure of Class III or IV of the NYHA classification&#xD;
&#xD;
               -  Uncontrolled angina, hypertension or arrhythmia&#xD;
&#xD;
               -  Myocardial infarction in past 6 months&#xD;
&#xD;
               -  Any uncontrolled or severe cardiovascular disease&#xD;
&#xD;
               -  Prior cerebrovascular event with persistent neurologic deficit&#xD;
&#xD;
          -  Medical conditions that, in the investigator's opinion, would impose excessive risk to&#xD;
             the subject.&#xD;
&#xD;
          -  Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy.&#xD;
&#xD;
          -  Systemic infection requiring IV antibiotic therapy within 7 days preceding the first&#xD;
             dose of study drug, or other severe infection.&#xD;
&#xD;
          -  Pregnant women are excluded from this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amir Fathi, 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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>August 15, 2017</last_update_submitted>
  <last_update_submitted_qc>August 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Amir Fathi</investigator_full_name>
    <investigator_title>Principal Investigators</investigator_title>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia (AML)</keyword>
  <keyword>Acute Myelocytic Leukemia</keyword>
  <keyword>Acute Myelogenous Leukemia</keyword>
  <keyword>Acute Granulocytic Leukemia</keyword>
  <keyword>Acute Non-Lymphocytic Leukemia</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>Lenalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02255162
org study id: 14-265
nct id: NCT02255162
lead sponsor: 
collaborator: 
has dmc: Yes
This research study is evaluating the safety and tolerability of the drug lenalidomide in
      combination with and following mismatched related donor microtransplantation in high risk AML
      patients in first remission. This study also aims to define the maximum tolerated dose (MTD)
      of lenalidomide given in this setting.

      Microtransplantation seeks to give the participant donor cells in hopes that those cells can
      attack the underlying cancer. However, since the donor cells do not replace all of the host
      cells, it can hopefully avoid many of the serious risks involved with standard transplant,
      including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the
      participant's normal body. Recent studies have suggested that lenalidomide can help aid donor
      cells to attack cancer when given after a stem cell transplant. This trial is trying to see
      if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part
      of microtransplantation.

      The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been
      approved for other uses such as in the treatment of other cancers including multiple myeloma
      and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has
      not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the
      Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact
      antitumor mechanism of action of lenalidomide is unknown.
After the screening procedures confirm that the participant is eligible to participate in the
      research study. The participant will be given a study drug-dosing calendar.

      The investigators are looking for the highest dose of the study drug that can be administered
      safely without severe or unmanageable side effects in participants, not everyone who
      participates in this research study will receive the same dose of the study drug. The dose
      given will depend on the number of participants who have been enrolled in the study prior and
      how well they have tolerated their doses. Participants will receive the following:

        -  Cytarabine

        -  Microtransplantation

        -  Lenalidomide
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
time frame: Baseline, 42 Days
measure: Disease Free Survival
time frame: 1 year
measure: Overall Survival
time frame: 1 Year
measure: To assess immunomodulatory effects of this combination through measurement of T cell subsets by flow cytometric techniques and through microchimerism analysis at multiple points on study
time frame: 2 Years
measure: To identify incidence and severity of acute and chronic graft versus host disease (GVHD).
time frame: 2 Years
measure: To detect and categorize, according to severity, the cumulative incidences of toxicities
time frame: 2 Years
arm group label: Lenalidomide
arm group type: Experimental
description: Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.
Participants will receive the following:
Cytarabine-intravenous, fixed dosage, given 5 times during cycle
HLA-mismatched stem-cell microtransplantation
Lenalidomide-administered daily per cycle
intervention type: Drug
intervention name: Lenalidomide
description: Patients will receive lenalidomide starting on day 6 of each post-remission cycle, following conclusion of cytarabine post-remission therapy on days 1-5. Following count recovery in the third post-remission cycle, patients will then receive lenalidomide daily as a maintenance therapy.
arm group label: Lenalidomide
other name: •Revlimid®
intervention type: Genetic
intervention name: HLA-mismatched stem-cell Microtransplantation
description: Patient will receive HLA-mismatched stem cell microtransplant infusion on day 6 of each post-remission cycle, following conclusion of course of cytarabine in each cycle.
arm group label: Lenalidomide
intervention type: Drug
intervention name: Cytarabine
description: Patients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle.
arm group label: Lenalidomide
other name: Cytosar-U ®
other name: 1-β-Arabinofuranosylcytosine
other name: Arabinosylcytosine
other name: Cytosine arabinoside
other name: Ara-C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amir Fathi, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Amir Fathi
investigator title: Principal Investigators
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Lenalidomide
sharing ipd: Undecided