<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/NCT01661400</url>
  </required_header>
  <id_info>
    <org_study_id>201209088</org_study_id>
    <nct_id>NCT01661400</nct_id>
  </id_info>
  <brief_title>Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors</brief_title>
  <acronym>ASCR</acronym>
  <official_title>Anti-Angiogenic Therapy After Autologous Stem Cell Rescue (ASCR) for Pediatric Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to determine whether taking either of two low dose&#xD;
      drugs that would prevent new blood vessels from growing after stem cell transplant is&#xD;
      feasible, and what the side effects of taking each of these drugs after autologous transplant&#xD;
      might be. The reason the investigators are looking at these drugs is because one of the&#xD;
      things that allows tumors to grow quickly is their ability to stimulate the growth of new&#xD;
      blood vessels. By suppressing the growth of new blood vessels after stem cell transplant, the&#xD;
      investigators hope to prevent the tumors from coming back or continuing to grow.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 26, 2012</start_date>
  <completion_date type="Anticipated">December 27, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 27, 2023</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>Safety as measured by absence of grade 4 or 5 non-hematological or grade 5 hematological toxicity</measure>
    <time_frame>Through 1 year post-transplant</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of major transplant related toxicities (Grades IV and IV)</measure>
    <time_frame>Within the first year of transplant</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best overall response</measure>
    <time_frame>86 days</time_frame>
    <description>Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Glioma</condition>
  <condition>Neuroectodermal Tumors, Primitive</condition>
  <condition>Wilms Tumor</condition>
  <condition>Rhabdomyosarcoma</condition>
  <condition>Sarcoma, Ewing</condition>
  <condition>Osteosarcoma</condition>
  <condition>Retinoblastoma</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metronomic Cyclophosphamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cyclophosphamide will be given PO once daily at 2.5 mg/kg/day for children &lt; 40kg or 100 mg daily for children &gt; 40kg beginning Day + 30 (30 days post transplant) and continue until at least Day +86</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thalidomide will be initiated at 3mg/kg PO daily beginning Day + 30 (30 days post transplant) and continue until Day +86</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metronomic Cyclophosphamide</intervention_name>
    <arm_group_label>Metronomic Cyclophosphamide</arm_group_label>
    <other_name>Cytoxan®</other_name>
    <other_name>CPM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thalidomide</intervention_name>
    <arm_group_label>Thalidomide</arm_group_label>
    <other_name>Thalomid®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have an original diagnosis, benefited by autologous transplantation,&#xD;
             confirmed by biopsy* of high-grade glial tumor, low-grade glial tumor, ependymoma,&#xD;
             medulloblastoma, primitive neuro-ectodermal tumor (PNET), Wilms' tumor,&#xD;
             rhabdomyosarcoma, Ewing's sarcoma, retinoblastoma, or miscellaneous poor-prognosis&#xD;
             solid tumors. Lymphomas and other lymphoid malignancies will not be studied in this&#xD;
             protocol.&#xD;
&#xD;
             * Brain stem glioma patients who have progressed after radiation therapy do not&#xD;
             require histologic confirmation. Brain stem gliomas are defined as intrinsic tumors of&#xD;
             the pons causing diffuse enlargement. These patients are diagnosed on clinical and&#xD;
             radiographic appearance of the lesion and the biopsy requirement will be waived for&#xD;
             this group.&#xD;
&#xD;
          -  Patient must be ≥ 6 months of age and ≤ 21 years of age at the time of study entry.&#xD;
&#xD;
          -  Patient must have a Karnofsky performance status or Lansky* play status ≥ 50&#xD;
&#xD;
             * For purpose of determining performance scores, wheelchair-bound patients will be&#xD;
             considered ambulatory.&#xD;
&#xD;
          -  Patient must have an adequate supply of stem cells for transplant harvested prior to&#xD;
             study enrollment, with adequate supply defined as 3 x 10^6 CD34+ cells/kg for&#xD;
             peripheral blood stem cells (PBSC). Cell mobilization method will be left up to the&#xD;
             treating physician's discretion and may include mobilization growth factor alone or&#xD;
             mobilization after chemotherapy. If patient is unable to mobilize the proper amount of&#xD;
             peripheral stem cells, bone marrow may be harvested as the source of hematopoietic&#xD;
             stem cells. In this instance, 3 x 10^8 mononuclear cells/kg will be considered&#xD;
             adequate. If necessary, a combination of peripheral stem cells and bone marrow can be&#xD;
             used.&#xD;
&#xD;
          -  Prior radiation therapy and/or chemotherapy, including cyclophosphamide, are&#xD;
             permitted.&#xD;
&#xD;
          -  Prior anti-angiogenic therapy, including thalidomide and oral cyclophosphamide, is&#xD;
             permitted.&#xD;
&#xD;
          -  If on corticosteroids for mass effect and/or edema related to the tumor, patient must&#xD;
             be on a stable or decreasing dose for at least 2 weeks prior to study entry.&#xD;
&#xD;
          -  Patient must have a life expectancy &gt; 3 months.&#xD;
&#xD;
          -  Patient must have an adequate bone marrow reserve as defined by:&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dl and&#xD;
&#xD;
               -  Peripheral absolute neutrophil count (ANC) ≥ 750/mm3&#xD;
&#xD;
          -  Patient must have adequate cardiac function tested within 4 weeks of study enrollment&#xD;
             as defined by:&#xD;
&#xD;
               -  Shortening fraction of ≥ 27% by echocardiogram or&#xD;
&#xD;
               -  Ejection fraction of ≥ 50% by radionuclide angiogram&#xD;
&#xD;
          -  Patient must have adequate pulmonary function tested within 4 weeks of study&#xD;
             enrollment as defined by:&#xD;
&#xD;
               -  Pulse oximetry &gt; 94% on room air or O2 by nasal cannula and&#xD;
&#xD;
               -  No evidence of dyspnea at rest.&#xD;
&#xD;
          -  Patient must have adequate hepatic function as defined by:&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age and&#xD;
&#xD;
               -  SGOT (AST) or SGPT (ALT) ≤ 2.5 x ULN (SGOT ≤ 4x ULN if on Zantac)&#xD;
&#xD;
          -  Patient must have adequate renal function as defined by:&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 mg/dl&#xD;
&#xD;
               -  Glomerular filtration rate (GFR), calculated via I-125 iothalamate clearance,&#xD;
                  24-hour creatinine clearance, or Schwartz formula*, ≥ 70 mL/min and ≥ 50&#xD;
                  mL/min/1.73 m2 done within 4 weeks of study entry&#xD;
&#xD;
               -  The Schwartz formula is an estimated glomerular filtration rate in children based&#xD;
                  upon serum creatinine and height. Height (Ht) should be measured in cm and serum&#xD;
                  creatinine (Cr) in mg/dL. Proportionality constant (k) is 0.55 for children and&#xD;
                  adolescent girls and 0.7 for adolescent boys aged 13-21. This constant is based&#xD;
                  upon a series of evaluations performed by Schwartz. Formula: GFR= (k x Ht)/Cr&#xD;
&#xD;
          -  Enrollment in the Celgene THALOMID REMSTM Program:&#xD;
&#xD;
               1. If enrolled in Arm III of this study, patient must be registered at the Celgene&#xD;
                  THALOMID REMSTM Program prior to day +30 post-ASCR.&#xD;
&#xD;
               2. If enrolled in Arm III of this study, patient must be willing to practice birth&#xD;
                  control as outlined in the THALOMID REMSTM Program from the beginning of the&#xD;
                  thalidomide treatment until at least 4 weeks following discontinuation of&#xD;
                  thalidomide therapy. Two reliable forms of contraception must be used&#xD;
                  simultaneously unless continuous abstinence from heterosexual sexual contact is&#xD;
                  chosen. Contraceptive methods must include at least one highly effective method&#xD;
                  (e.g. oral contraceptive pills, injections, hormonal patches, IUD, or implants),&#xD;
                  AND one additional effective barrier method (e.g. latex condom, diaphragm,&#xD;
                  cervical cap).&#xD;
&#xD;
                  If hormonal or IUD contraception is medically contraindicated, another highly&#xD;
                  effective method or two barrier methods must be used at the same time.&#xD;
&#xD;
               3. Pregnancy surveillance:&#xD;
&#xD;
             i. Patient must have a negative in office pregnancy test sensitive to within 50 mIU/mL&#xD;
             (serum or urine) within 24 hours prior to beginning thalidomide even if continuous&#xD;
             abstinence is the preferred method of birth control. ii. A pregnancy test must be&#xD;
             performed weekly during the first 4 weeks of therapy and repeated monthly for patients&#xD;
             with regular menses or every 2 weeks for patients with irregular menses iii. Negative&#xD;
             pregnancy tests are valid for only 7 days. iv. If irregular bleeding or skipped&#xD;
             menses, pregnancy test should be performed and pregnancy counseling given. v. If&#xD;
             pregnancy occurs during treatment, thalidomide must be immediately discontinued. Any&#xD;
             suspected lethal exposure must be reported immediately to Celgene Customer Care Center&#xD;
             at 1-888-423-5346, and the patient referred to an OB/GYN experienced in reproductive&#xD;
             toxicity for further evaluation and counseling.&#xD;
&#xD;
          -  Patient (or legally authorized representative) must be able to understand and willing&#xD;
             to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have any active, uncontrolled cardiac, hepatic, renal, or psychiatric&#xD;
             disease defined as ≥ grade 3 based on NCI Common Terminology Criteria for Adverse&#xD;
             Events v4.0 (CTCAE).&#xD;
&#xD;
          -  Patient must not be receiving any other investigational agents.&#xD;
&#xD;
          -  Patient must not have any active infection or concurrent illness obscuring toxicity or&#xD;
             dangerously altering drug metabolism.&#xD;
&#xD;
          -  Patient must not have any thromboembolic event (deep vein thrombosis or pulmonary&#xD;
             embolism) less than 3 weeks prior to enrollment.&#xD;
&#xD;
          -  Patient must not have a history of allergic reactions attributed to compounds of&#xD;
             similar chemical or biologic composition to any of the agents used in the study.&#xD;
&#xD;
          -  Patient must not be pregnant or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Cluster, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>January 29, 2023</last_update_submitted>
  <last_update_submitted_qc>January 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glioma includes ependymoma and medulloblastoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Osteosarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Neuroectodermal Tumors</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive</mesh_term>
    <mesh_term>Wilms Tumor</mesh_term>
    <mesh_term>Retinoblastoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive, Peripheral</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalidomide</mesh_term>
    <mesh_term>Cyclophosphamide</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/NCT01661400
org study id: 201209088
nct id: NCT01661400
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to determine whether taking either of two low dose
      drugs that would prevent new blood vessels from growing after stem cell transplant is
      feasible, and what the side effects of taking each of these drugs after autologous transplant
      might be. The reason the investigators are looking at these drugs is because one of the
      things that allows tumors to grow quickly is their ability to stimulate the growth of new
      blood vessels. By suppressing the growth of new blood vessels after stem cell transplant, the
      investigators hope to prevent the tumors from coming back or continuing to grow.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety as measured by absence of grade 4 or 5 non-hematological or grade 5 hematological toxicity
time frame: Through 1 year post-transplant
measure: Incidence of major transplant related toxicities (Grades IV and IV)
time frame: Within the first year of transplant
measure: Best overall response
time frame: 86 days
description: Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.
arm group label: Control
arm group type: No Intervention
description: No intervention
arm group label: Metronomic Cyclophosphamide
arm group type: Experimental
description: Cyclophosphamide will be given PO once daily at 2.5 mg/kg/day for children < 40kg or 100 mg daily for children > 40kg beginning Day + 30 (30 days post transplant) and continue until at least Day +86
arm group label: Thalidomide
arm group type: Experimental
description: Thalidomide will be initiated at 3mg/kg PO daily beginning Day + 30 (30 days post transplant) and continue until Day +86
intervention type: Drug
intervention name: Metronomic Cyclophosphamide
arm group label: Metronomic Cyclophosphamide
other name: Cytoxan®
other name: CPM
intervention type: Drug
intervention name: Thalidomide
arm group label: Thalidomide
other name: Thalomid®
criteria: 
gender: All
minimum age: 6 Months
maximum age: 21 Years
healthy volunteers: No
last name: Andrew Cluster, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Osteosarcoma
mesh term: Rhabdomyosarcoma
mesh term: Neuroectodermal Tumors
mesh term: Neuroectodermal Tumors, Primitive
mesh term: Wilms Tumor
mesh term: Retinoblastoma
mesh term: Sarcoma, Ewing
mesh term: Neuroectodermal Tumors, Primitive, Peripheral
mesh term: Thalidomide
mesh term: Cyclophosphamide
sharing ipd: No