<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/NCT03032783</url>
  </required_header>
  <id_info>
    <org_study_id>16D.606</org_study_id>
    <nct_id>NCT03032783</nct_id>
  </id_info>
  <brief_title>A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies-Increasing GVT Effects Without Increasing Toxicity</brief_title>
  <official_title>A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies-Increasing GVT Effects Without Increasing Toxicity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Cancer Center at Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies the how well donor stem cell transplant works in treating&#xD;
      patients with high risk hematologic malignancies. Giving total-body irradiation and&#xD;
      chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone&#xD;
      marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop&#xD;
      the patient's immune system from rejecting the donor's stem cells. When the healthy stem&#xD;
      cells from a donor are infused into the patient they may help the patient's bone marrow make&#xD;
      stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may&#xD;
      also replace the patient's immune cells and help destroy any remaining cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      1. To assess 2 year probability of OS in high risk patients undergoing a myeloablative 2 step&#xD;
      HSCT utilizing strategies to decrease relapse.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        1. To assess relapse incidence at 2 years post-HSCT of patients undergoing treatment on&#xD;
           this protocol.&#xD;
&#xD;
        2. To assess regimen related toxicity and GVHD incidence at 2 years post-HSCT and severity&#xD;
           in patients undergoing treatment on this protocol.&#xD;
&#xD;
        3. To assess the consistency and pace of engraftment.&#xD;
&#xD;
        4. To assess the pace of T cell and B cell immune recovery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">January 13, 2025</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>Overall Survival (OS)</measure>
    <time_frame>At two years</time_frame>
    <description>Will be tested using an exact one-sided binomial test with alpha 0.05. The trial will be considered successful if the null hypothesis of 45% 2-year OS is rejected. In addition, the exact binomial 95% confidence interval for 2-year OS will be computed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft failure</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Should be less than 10%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of non-relapse mortality</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Should be less than 20% at 100 days</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">63</enrollment>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8 and and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide IV on days -3 and -2, tacrolimus IV beginning on day -1 and then orally at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV twice daily on days -1 to 28. Patients undergo Allogeneic Hematopoietic Stem Cell Transplantation on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total-Body Irradiation</intervention_name>
    <description>Undergo Total Body Irradiation</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>Total Body Irradiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Donor Lymphocyte Infusion</intervention_name>
    <description>Undergo Donor Lymphocyte Infusion</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>DLI</other_name>
    <other_name>Donor Leukocyte Infusion</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate</other_name>
    <other_name>2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate</other_name>
    <other_name>6055-19-2</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Clafen</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>Fujimycin</other_name>
    <other_name>717865</other_name>
    <other_name>109581-93-3</other_name>
    <other_name>Hecoria</other_name>
    <other_name>Prograf</other_name>
    <other_name>Protopic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>115007-34-6</other_name>
    <other_name>128794-94-5</other_name>
    <other_name>724229</other_name>
    <other_name>Cellcept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo Hematopoietic Stem Cell Transplantation</description>
    <arm_group_label>Treatment (TBI, DLI, chemotherapy, HSCT)</arm_group_label>
    <other_name>HSCT</other_name>
    <other_name>HSC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        This treatment is for patients with high risk hematologic malignancies. High risk is&#xD;
        defined as:&#xD;
&#xD;
          -  Any patient with a hematologic malignancy in which allogeneic HSCT is pursued with the&#xD;
             expectation of cure. Patients may have post-treatment residual disease, but the&#xD;
             disease should be stable or minimally progressive and must be responsive to&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Any patient with an untreated hematologic malignancy in which allogeneic HSCT is&#xD;
             thought to be the sole or the best option for cure and in Patients without morphologic&#xD;
             evidence of disease but with high risk features which would predict for relapsed&#xD;
             despite remission at HSCT such as adverse cytogenetics, 3rd or greater CR, or failure&#xD;
             to recover peripheral blood counts to normal ranges. While these patients do not have&#xD;
             detectable disease by current methods, like all patients they have non-detectable&#xD;
             disease which in their case is highly aggressive.&#xD;
&#xD;
          -  Patients with uncommon diagnoses in which allogeneic HSCT is thought to be beneficial&#xD;
             but are no comparable to the majority of patients on this protocol will not be counted&#xD;
             in the statistical aims of the study and will be reported descriptively. The PI and at&#xD;
             least one Co-I must document this exception in the study binder and the rationale for&#xD;
             descriptive report. An example of a patient who may meet this criteria is someone with&#xD;
             a malignancy that is an overlap of two different diagnoses or one whose malignancy is&#xD;
             difficult to categorize. While this circumstance is expected to be rare, it will&#xD;
             prevent patients with rare diagnoses to be treated off study and it will help maintain&#xD;
             homogeneity of the study population.&#xD;
&#xD;
          -  Patients must have one related donor who is HLA mismatched in the GVHD direction at&#xD;
             two or more HLA loci (except as described below)&#xD;
&#xD;
          -  Patients must have adequate organ function:&#xD;
&#xD;
          -  Left Ventricular Ejection Fraction (LVEF) of ≥50%&#xD;
&#xD;
          -  DLCO (adjusted for hemoglobin) ≥50% of predicted and FEV-1 ≥50%&#xD;
&#xD;
          -  Adequate liver function as defined by a serum bilirubin ≤1.8, Aspartate&#xD;
             aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal&#xD;
             (ULN)&#xD;
&#xD;
          -  Creatinine clearance of ≥ 60ml/min&#xD;
&#xD;
          -  Karnofsky Performance Status (KPS) of ≥80% on the modified KPS tool (see Appendix)&#xD;
&#xD;
          -  Patients must be willing to use contraception if they have childbearing potential&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
          -  Age ≥ 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Modified KPS of &lt;80%&#xD;
&#xD;
          -  &gt; 5 Comorbidity Points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT&#xD;
             CI) (See Appendix) (Patients with greater than 5 points will be allowed for trial with&#xD;
             approval of the PI and at least 1 Co-I not on the primary care team of the patient.)&#xD;
             this is an adjustment to account for healthy patients who meet the spirit of this&#xD;
             protocol but have histories that result in higher than HCT-CI 5 points. An example is&#xD;
             a patient with a solid tumor malignancy in their remote history (adds 3 points to&#xD;
             HCT-CI total) where the treatment for the malignancy occurred years to decades before&#xD;
             and there has been complete recovery of toxicities.&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV) positive&#xD;
&#xD;
          -  Active involvement of the central nervous system with malignancy&#xD;
&#xD;
          -  Psychiatric disorder that would preclude patients from signing an informed consent&#xD;
&#xD;
          -  Pregnancy, or unwillingness to use contraception if they have childbearing potential&#xD;
&#xD;
          -  Patients with life expectancy of ≤ 6 months for reasons other than their underlying&#xD;
             hematologic/oncologic disorder&#xD;
&#xD;
          -  Alemtuzumab treatment within 8 weeks of HSCT admission&#xD;
&#xD;
          -  ATG within 8 weeks of HSCT administration&#xD;
&#xD;
          -  Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses&#xD;
             specified in the treatment plan.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Usama Gergis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sidney Kimmel Cancer Center at Thomas Jefferson University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Usama Gergis, MD</last_name>
    <phone>215-955-8874</phone>
    <email>usama.gergis@jefferson.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sidney Kimmel Cancer Center at Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>USAMA GERGIS, MD</last_name>
      <phone>215-955-8874</phone>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://hospitals.jefferson.edu/</url>
    <description>Thomas Jefferson University Hospital</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>May 25, 2023</last_update_submitted>
  <last_update_submitted_qc>May 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 26, 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>Hematologic Neoplasms</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>Tacrolimus</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/NCT03032783
org study id: 16D.606
nct id: NCT03032783
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This phase II trial studies the how well donor stem cell transplant works in treating
      patients with high risk hematologic malignancies. Giving total-body irradiation and
      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. It may also stop
      the patient's immune system from rejecting the donor's stem 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. The donated stem cells may
      also replace the patient's immune cells and help destroy any remaining cancer cells.
Primary Objective:

      1. To assess 2 year probability of OS in high risk patients undergoing a myeloablative 2 step
      HSCT utilizing strategies to decrease relapse.

      Secondary Objective:

        1. To assess relapse incidence at 2 years post-HSCT of patients undergoing treatment on
           this protocol.

        2. To assess regimen related toxicity and GVHD incidence at 2 years post-HSCT and severity
           in patients undergoing treatment on this protocol.

        3. To assess the consistency and pace of engraftment.

        4. To assess the pace of T cell and B cell immune recovery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS)
time frame: At two years
description: Will be tested using an exact one-sided binomial test with alpha 0.05. The trial will be considered successful if the null hypothesis of 45% 2-year OS is rejected. In addition, the exact binomial 95% confidence interval for 2-year OS will be computed.
measure: Incidence of graft failure
time frame: Up to 2 years
description: Should be less than 10%
measure: Incidence of non-relapse mortality
time frame: Up to 2 years
description: Should be less than 20% at 100 days
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
arm group type: Experimental
description: Patients undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8 and and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide IV on days -3 and -2, tacrolimus IV beginning on day -1 and then orally at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV twice daily on days -1 to 28. Patients undergo Allogeneic Hematopoietic Stem Cell Transplantation on day 0.
intervention type: Radiation
intervention name: Total-Body Irradiation
description: Undergo Total Body Irradiation
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: Total Body Irradiation
intervention type: Procedure
intervention name: Donor Lymphocyte Infusion
description: Undergo Donor Lymphocyte Infusion
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: DLI
other name: Donor Leukocyte Infusion
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: (-)-Cyclophosphamide
other name: 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate
other name: 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
other name: 6055-19-2
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Clafen
other name: CP monohydrate
other name: CTX
other name: Cycloblastin
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: WR- 138719
intervention type: Drug
intervention name: Tacrolimus
description: Given IV
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: Fujimycin
other name: 717865
other name: 109581-93-3
other name: Hecoria
other name: Prograf
other name: Protopic
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given IV
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: 115007-34-6
other name: 128794-94-5
other name: 724229
other name: Cellcept
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo Hematopoietic Stem Cell Transplantation
arm group label: Treatment (TBI, DLI, chemotherapy, HSCT)
other name: HSCT
other name: HSC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Usama Gergis, MD
role: Principal Investigator
affiliation: Sidney Kimmel Cancer Center at Thomas Jefferson University
last name: Usama Gergis, MD
phone: 215-955-8874
email: usama.gergis@jefferson.edu
facility: 
status: Recruiting
contact: 
country: United States
url: http://hospitals.jefferson.edu/
description: Thomas Jefferson University Hospital
responsible party type: Sponsor
mesh term: Hematologic Neoplasms
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Tacrolimus