<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/NCT02248597</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00029210</org_study_id>
    <secondary_id>NCI-2014-01898</secondary_id>
    <secondary_id>CCCWFU 97214</secondary_id>
    <secondary_id>P30CA012197</secondary_id>
    <nct_id>NCT02248597</nct_id>
  </id_info>
  <brief_title>Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases</brief_title>
  <official_title>Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</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 pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in&#xD;
      treating patients with hematological diseases. Giving chemotherapy before a donor stem cell&#xD;
      transplant helps stop the growth of cells in the bone marrow, including normal blood-forming&#xD;
      cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused&#xD;
      into the patient they may help the patient's bone marrow make stem cells, red blood cells,&#xD;
      white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an&#xD;
      immune response against the body's normal cells (called graft-versus-host disease). Giving&#xD;
      cyclophosphamide after the transplant may stop this from happening.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide&#xD;
      results in 60% or better disease free survival (DFS) at 12 months at our institution.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse&#xD;
      mortality, and relapse.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily&#xD;
      (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV&#xD;
      every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity&#xD;
      conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also&#xD;
      receive cyclophosphamide IV QD on days -3 and -2&#xD;
&#xD;
      TRANSPLANT: Patients undergo stem cell transplant on day 0.&#xD;
&#xD;
      GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days&#xD;
      5-180, and mycophenolate mofetil on days 5-35.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2015</start_date>
  <completion_date type="Actual">January 18, 2023</completion_date>
  <primary_completion_date type="Actual">January 18, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>12 month disease free survival probability</measure>
    <time_frame>At 12 months</time_frame>
    <description>The proportion of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of acute GvHD</measure>
    <time_frame>At 12 months</time_frame>
    <description>Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of chronic GvHD</measure>
    <time_frame>At 12 months</time_frame>
    <description>Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 12 months</time_frame>
    <description>The survival function will be estimated and plotted using the method of Kaplan and Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse (or death)</measure>
    <time_frame>At 12 months</time_frame>
    <description>Calculating the proportion of patients who experience death by one year and construct a corresponding 95% confidence interval using the normal approximation for binomial proportions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free mortality</measure>
    <time_frame>At 12 months</time_frame>
    <description>The cumulative incidence function in the presence of relapse will be estimated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Graft Versus Host Disease</condition>
  <condition>Hematopoietic/Lymphoid Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2&#xD;
TRANSPLANT: Patients undergo stem cell transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fludarabine phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <other_name>2-F-ara-AMP</other_name>
    <other_name>Beneflur</other_name>
    <other_name>Fludara</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <other_name>BSF</other_name>
    <other_name>BU</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeloleukon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <other_name>CPM</other_name>
    <other_name>CTX</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Endoxan</other_name>
    <other_name>Endoxana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>allogeneic hematopoietic stem cell transplantation</intervention_name>
    <description>Undergo myeloablative or reduced intensity allogeneic stem cell transplant</description>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tacrolimus</intervention_name>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <other_name>FK 506</other_name>
    <other_name>Prograf</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mycophenolate mofetil</intervention_name>
    <arm_group_label>Treatment (stem cell transplant with GVHD prophylaxis)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>MMF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant&#xD;
             consistent with the standard of care&#xD;
&#xD;
          -  Remission of any acute hematologic malignancy or adequate disease control for chronic&#xD;
             malignancies.&#xD;
&#xD;
          -  Ages 18-69 years old.&#xD;
&#xD;
          -  Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant organ dysfunction defined as: LV EF &lt; 50% (evaluated by echocardiogram or&#xD;
             MRI), DLCO or FEV1 &lt; 65% predicted, AST/ALT &gt; 2.5 x ULN, Bilirubin &gt; 1.5 x ULN, Serum&#xD;
             creatinine &gt; 2mg/dL, dialysis, or prior renal transplant&#xD;
&#xD;
          -  HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or&#xD;
             human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)&#xD;
&#xD;
          -  Positive pregnancy test for women of childbearing age.&#xD;
&#xD;
          -  Major anticipated illness or organ failure incompatible with survival form transplant.&#xD;
&#xD;
          -  Severe psychiatric illness or mental deficiency sufficiently severe as to make&#xD;
             compliance with the transplant treatment unlikely and informed consent impossible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dianna S. Howard</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Comprehensive Cancer Center of Wake Forest University</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</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>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 22, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT02248597/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>August 17, 2023</submitted>
    <returned>September 14, 2023</returned>
  </pending_results>
  <!-- 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/NCT02248597
org study id: IRB00029210
secondary id: NCI-2014-01898
secondary id: CCCWFU 97214
secondary id: P30CA012197
nct id: NCT02248597
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in
      treating patients with hematological diseases. Giving chemotherapy before a donor stem cell
      transplant helps stop the growth of cells in the bone marrow, including normal blood-forming
      cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused
      into the patient they may help the patient's bone marrow make stem cells, red blood cells,
      white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an
      immune response against the body's normal cells (called graft-versus-host disease). Giving
      cyclophosphamide after the transplant may stop this from happening.
PRIMARY OBJECTIVES:

      I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide
      results in 60% or better disease free survival (DFS) at 12 months at our institution.

      SECONDARY OBJECTIVES:

      I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse
      mortality, and relapse.

      OUTLINE:

      PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily
      (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV
      every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity
      conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also
      receive cyclophosphamide IV QD on days -3 and -2

      TRANSPLANT: Patients undergo stem cell transplant on day 0.

      GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days
      5-180, and mycophenolate mofetil on days 5-35.

      After completion of study treatment, patients are followed up periodically for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 12 month disease free survival probability
time frame: At 12 months
description: The proportion of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
measure: Rate of acute GvHD
time frame: At 12 months
description: Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.
measure: Rate of chronic GvHD
time frame: At 12 months
description: Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.
measure: Overall survival
time frame: At 12 months
description: The survival function will be estimated and plotted using the method of Kaplan and Meier.
measure: Relapse (or death)
time frame: At 12 months
description: Calculating the proportion of patients who experience death by one year and construct a corresponding 95% confidence interval using the normal approximation for binomial proportions.
measure: Relapse-free mortality
time frame: At 12 months
description: The cumulative incidence function in the presence of relapse will be estimated.
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
arm group type: Experimental
description: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation
intervention type: Drug
intervention name: fludarabine phosphate
description: Given IV
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
other name: 2-F-ara-AMP
other name: Beneflur
other name: Fludara
intervention type: Drug
intervention name: busulfan
description: Given IV
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
other name: BSF
other name: BU
other name: Misulfan
other name: Mitosan
other name: Myeloleukon
intervention type: Drug
intervention name: cyclophosphamide
description: Given IV
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
other name: CPM
other name: CTX
other name: Cytoxan
other name: Endoxan
other name: Endoxana
intervention type: Procedure
intervention name: allogeneic hematopoietic stem cell transplantation
description: Undergo myeloablative or reduced intensity allogeneic stem cell transplant
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
intervention type: Drug
intervention name: tacrolimus
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
other name: FK 506
other name: Prograf
intervention type: Drug
intervention name: mycophenolate mofetil
arm group label: Treatment (stem cell transplant with GVHD prophylaxis)
other name: Cellcept
other name: MMF
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: No
last name: Dianna S. Howard
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Graft vs Host Disease
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Busulfan
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Tacrolimus
provided document: 
submitted: August 17, 2023
returned: September 14, 2023