<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/NCT01677949</url>
  </required_header>
  <id_info>
    <org_study_id>2011LS158</org_study_id>
    <secondary_id>HM2012-05</secondary_id>
    <nct_id>NCT01677949</nct_id>
  </id_info>
  <brief_title>Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia</brief_title>
  <official_title>A Phase II Trial Investigating Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Masonic Cancer Center, University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Masonic Cancer Center, University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Design:&#xD;
&#xD;
      This is a two-stage Phase II trial investigating the efficacy of Clofarabine,&#xD;
      Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual&#xD;
      disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the&#xD;
      study treatment in eliminating the presence of minimal residual disease without causing a&#xD;
      significant delay of allo-HCT due to treatment related toxicity. The intent of this study is&#xD;
      to allow patients to proceed to transplant (independent of this study) within 42 days of Day&#xD;
      1 of Clofarabine based therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML).&#xD;
      Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49&#xD;
      patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in&#xD;
      stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on&#xD;
      success of clearing MRD, proceeding to transplant within 42 days and without excessive&#xD;
      toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients&#xD;
      enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Slow accrual&#xD;
  </why_stopped>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients Unable to Proceed to Transplantation</measure>
    <time_frame>Between Day 30 and Day 42</time_frame>
    <description>The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (&lt;0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Pre-Transplant Chemotherapy-Induced Aplasia</measure>
    <time_frame>After Day 42</time_frame>
    <description>defined as greater than 42 days after infusion of chemotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Infectious Complications</measure>
    <time_frame>Day 1 Through Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-Related Mortality After Transplant</measure>
    <time_frame>Day 100</time_frame>
    <description>In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-Free Survival After Transplant</measure>
    <time_frame>1 Year</time_frame>
    <description>The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Leukemic Relapse After Transplant</measure>
    <time_frame>Day 100</time_frame>
    <description>The return of disease after its apparent recovery/cessation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>ALL patients receiving transplant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute lymphoblastic leukemia (ALL) along with Clofarabine, Etoposide and Cyclophosphamide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AML patients receiving transplant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute myeloid leukemia (AML) along with Clofarabine, Etoposide and Cyclophosphamide.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clofarabine</intervention_name>
    <description>Days 1-5: Clofarabine 30 mg/m^2 for 0-30 years of age or 20 mg/m^2 for &gt; 30 years of age intravenously (IV) over 2 hours</description>
    <arm_group_label>ALL patients receiving transplant</arm_group_label>
    <arm_group_label>AML patients receiving transplant</arm_group_label>
    <other_name>Clolar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Days 1-5: Etoposide 100mg/m^2 IV over 2 hours</description>
    <arm_group_label>ALL patients receiving transplant</arm_group_label>
    <arm_group_label>AML patients receiving transplant</arm_group_label>
    <other_name>Eposin</other_name>
    <other_name>Etopophos</other_name>
    <other_name>Vepesid</other_name>
    <other_name>VP-16</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Days 1-5: Cyclophosphamide 300 mg/m^2 as a 30-60 minute infusion</description>
    <arm_group_label>ALL patients receiving transplant</arm_group_label>
    <arm_group_label>AML patients receiving transplant</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>allogeneic hematopoietic cell transplantation</intervention_name>
    <description>Between Days 28 and 42: infused independent of this study</description>
    <arm_group_label>ALL patients receiving transplant</arm_group_label>
    <arm_group_label>AML patients receiving transplant</arm_group_label>
    <other_name>allo-HCT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with&#xD;
             &lt;5% blasts in the bone marrow (M1) by morphology and that meets one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Flow cytometric evidence of MRD (≥ 0.1% leukemic blasts for ALL or &lt;5% leukemic&#xD;
                  blasts for AML detected in the bone marrow) OR&#xD;
&#xD;
               -  Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed&#xD;
                  within 7 days&#xD;
&#xD;
               -  AND with the intent of going on to an allogeneic hematopoietic cell&#xD;
                  transplantation (allo-HCT) independent of this study&#xD;
&#xD;
          -  Age 0 to 60 years&#xD;
&#xD;
          -  Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play&#xD;
             Score ≥ 50 for patients under 16 years of age&#xD;
&#xD;
          -  Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling&#xD;
             investigator&#xD;
&#xD;
          -  Have acceptable organ function as defined within 7 days of study registration:&#xD;
&#xD;
               -  Renal: creatinine clearance ≥70mL/min/1.73m2 or serum creatinine based on&#xD;
                  age/gender&#xD;
&#xD;
               -  Hepatic: aspartate aminotransferase (ALT) &lt; 5 x upper limit of normal (ULN) and&#xD;
                  total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age&#xD;
&#xD;
               -  Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram (ECHO/MUGA)&#xD;
&#xD;
          -  Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14&#xD;
             days must have elapsed from prior chemotherapy; at least 7 days must have elapsed&#xD;
             since receiving biological therapy.&#xD;
&#xD;
        Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth&#xD;
        factor and at least 14 days since pegfilgrastim (Neulasta®) administration.&#xD;
&#xD;
          -  Sexually active females of child bearing potential must agree to use adequate&#xD;
             contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],&#xD;
             surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration&#xD;
             of treatment and for 2 months after the last dose of chemotherapy. Sexually active men&#xD;
             must agree to use barrier contraceptive for the duration of treatment and for 2 months&#xD;
             after the last dose of chemotherapy.&#xD;
&#xD;
          -  Voluntary written consent before performance of any study-related procedure not part&#xD;
             of normal medical care, with the understanding that consent may be withdrawn by the&#xD;
             subject at any time without prejudice to future medical care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute Promyelocytic Leukemia (APL)&#xD;
&#xD;
          -  Active central nervous system (CNS) leukemia or known chloromatous disease&#xD;
&#xD;
          -  Receiving or plans to receive concomitant chemotherapy, radiation therapy;&#xD;
             immunotherapy or other anti-cancer therapy other than is specified in the protocol&#xD;
&#xD;
          -  Systemic fungal, bacterial, viral, or other infection not controlled (defined as&#xD;
             exhibiting ongoing signs/symptoms related to the infection and without improvement,&#xD;
             despite appropriate antibiotics or other treatment)&#xD;
&#xD;
          -  Pregnant or lactating. The agents used in this study are known to be teratogenic to a&#xD;
             fetus and there is no information on the excretion of agents into breast milk. All&#xD;
             females of childbearing potential must have a blood test or urine study within 2 weeks&#xD;
             prior to registration to rule out pregnancy.&#xD;
&#xD;
          -  Known allergy to any of the agents or their ingredients used in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Burke, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Masonic Cancer Center, University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Masonic Cancer Center, University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>November 29, 2017</last_update_submitted>
  <last_update_submitted_qc>November 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2017</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>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Neoplasm, Residual</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Clofarabine</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/NCT01677949
org study id: 2011LS158
secondary id: HM2012-05
nct id: NCT01677949
lead sponsor: 
has dmc: Yes
Study Design:

      This is a two-stage Phase II trial investigating the efficacy of Clofarabine,
      Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual
      disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the
      study treatment in eliminating the presence of minimal residual disease without causing a
      significant delay of allo-HCT due to treatment related toxicity. The intent of this study is
      to allow patients to proceed to transplant (independent of this study) within 42 days of Day
      1 of Clofarabine based therapy.
Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML).
      Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49
      patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in
      stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on
      success of clearing MRD, proceeding to transplant within 42 days and without excessive
      toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients
      enrolled.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients Unable to Proceed to Transplantation
time frame: Between Day 30 and Day 42
description: The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (<0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.
measure: Rate of Pre-Transplant Chemotherapy-Induced Aplasia
time frame: After Day 42
description: defined as greater than 42 days after infusion of chemotherapy
measure: Rate of Infectious Complications
time frame: Day 1 Through Day 30
measure: Treatment-Related Mortality After Transplant
time frame: Day 100
description: In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
measure: Disease-Free Survival After Transplant
time frame: 1 Year
description: The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
measure: Rate of Leukemic Relapse After Transplant
time frame: Day 100
description: The return of disease after its apparent recovery/cessation.
arm group label: ALL patients receiving transplant
arm group type: Experimental
description: Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute lymphoblastic leukemia (ALL) along with Clofarabine, Etoposide and Cyclophosphamide.
arm group label: AML patients receiving transplant
arm group type: Experimental
description: Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute myeloid leukemia (AML) along with Clofarabine, Etoposide and Cyclophosphamide.
intervention type: Drug
intervention name: Clofarabine
description: Days 1-5: Clofarabine 30 mg/m^2 for 0-30 years of age or 20 mg/m^2 for > 30 years of age intravenously (IV) over 2 hours
arm group label: ALL patients receiving transplant
arm group label: AML patients receiving transplant
other name: Clolar
intervention type: Drug
intervention name: Etoposide
description: Days 1-5: Etoposide 100mg/m^2 IV over 2 hours
arm group label: ALL patients receiving transplant
arm group label: AML patients receiving transplant
other name: Eposin
other name: Etopophos
other name: Vepesid
other name: VP-16
intervention type: Drug
intervention name: Cyclophosphamide
description: Days 1-5: Cyclophosphamide 300 mg/m^2 as a 30-60 minute infusion
arm group label: ALL patients receiving transplant
arm group label: AML patients receiving transplant
other name: Cytoxan
intervention type: Biological
intervention name: allogeneic hematopoietic cell transplantation
description: Between Days 28 and 42: infused independent of this study
arm group label: ALL patients receiving transplant
arm group label: AML patients receiving transplant
other name: allo-HCT
criteria: 
gender: All
minimum age: N/A
maximum age: 60 Years
healthy volunteers: No
last name: Michael Burke, M.D.
role: Principal Investigator
affiliation: Masonic Cancer Center, University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Neoplasm, Residual
mesh term: Cyclophosphamide
mesh term: Etoposide
mesh term: Clofarabine