<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/NCT04503616</url>
  </required_header>
  <id_info>
    <org_study_id>20-00136</org_study_id>
    <nct_id>NCT04503616</nct_id>
  </id_info>
  <brief_title>Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention</brief_title>
  <official_title>A Phase IB-II Study Of High-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus for the Prevention of Graft-Versus-Host Disease (GvHD) Following Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm, open label, optimal 2-stage Simon design phase Ib-II clinical trial.&#xD;
      Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or&#xD;
      second-degree haploidentical donor are eligible for the study if they meet the standard&#xD;
      criteria defined in our institutional standard operation procedures (SOPs), meet all&#xD;
      inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive&#xD;
      non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by&#xD;
      peripheral blood hematopoietic stem cells. Patients will receive cyclophosphamide, abatacept,&#xD;
      and short-duration tacrolimus for GvHD prophylaxis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 16, 2020</start_date>
  <completion_date type="Anticipated">June 20, 2024</completion_date>
  <primary_completion_date type="Actual">December 14, 2022</primary_completion_date>
  <phase>Phase 1/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>
    <intervention_model_description>Interventional, non-randomized open label, 2- stage optimal Simon design with interim futility analysis.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative Incidence of Grade II-IV Acute GvHD by Day +120</measure>
    <time_frame>120 days</time_frame>
    <description>The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.&#xD;
Overall Grades of Acute GvHD:&#xD;
0 = none;&#xD;
= mild;&#xD;
= moderate;&#xD;
= severe;&#xD;
= life threatening</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative Incidence of Chronic GvHD</measure>
    <time_frame>Day 365</time_frame>
    <description>The first day of chronic GvHD will be used to calculate the cumulative incidence of chronic GvHD. This endpoint will be evaluated through day +365 post-transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Incidence of Primary Graft Failure</measure>
    <time_frame>Day 45</time_frame>
    <description>Graft failure is defined as failure to achieve neutrophil engraftment by day +28 or lack of donor chimerism &gt; 50% by day 45, not due to the underlying malignancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Incidence of Poor Graft Function</measure>
    <time_frame>Day 28</time_frame>
    <description>Poor Graft Function defined by at least 2 of the following 3 criteria: Hemoglobin &lt; 8 g/dL, ANC &lt; 0.5 x 109/L, and platelets &lt; 20 x 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Secondary Graft Failure</measure>
    <time_frame>Day 730</time_frame>
    <description>Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism &lt; 5%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment-Related Deaths</measure>
    <time_frame>Day 730</time_frame>
    <description>Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse Rate</measure>
    <time_frame>Day 730</time_frame>
    <description>Evaluated to day +730 and defined as the percentage of patients in whom the disease for which transplant is performed becomes evident by methods of disease detection after the transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GvHD and Relapse-Free Survival (GRFS)</measure>
    <time_frame>Day 730</time_frame>
    <description>Evaluated to day +730 and defined as the percentage of participants who are without reported grade III-IV acute GvHD, without chronic GvHD requiring systemic therapy, and have not experienced relapse or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Day 730</time_frame>
    <description>Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Graft-versus-host Disease</condition>
  <arm_group>
    <arm_group_label>HSCT Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention</intervention_name>
    <description>Cyclophosphamide 50 mg/kg IV over 2 hours on Day +3 and +4 Abatacept 10 mg/kg IV on days +5, +14, and +28 Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on day +5. May switch to oral when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Treatment is discontinued on day +60 after a 4 week-taper</description>
    <arm_group_label>HSCT Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. Karnofsky score ≥ 70%&#xD;
&#xD;
          3. No evidence of progressive bacterial, viral, or fungal infection&#xD;
&#xD;
          4. Creatinine clearance &gt; 50 mL/min/1.72m2&#xD;
&#xD;
          5. Total bilirubin, ALT and AST &lt; 2 x the upper limit of normal (except for diagnosed&#xD;
             Gilbert's syndrome)&#xD;
&#xD;
          6. Alkaline phosphatase ≤ 250 IU/L&#xD;
&#xD;
          7. Left Ventricular Ejection Fraction (LVEF) &gt; 45%&#xD;
&#xD;
          8. Adjusted Carbon Monoxide Diffusing Capacity (DLCO) &gt; 60%&#xD;
&#xD;
          9. Negative HIV serology&#xD;
&#xD;
         10. Negative pregnancy test: confirmation per negative serum β-human chorionic&#xD;
             gonadotropin (β-hCG) for women of childbearing age and potential.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.&#xD;
&#xD;
          2. Pregnant or nursing females or women of child bearing age or potential, who are&#xD;
             unwilling to completely abstain from heterosexual sex or practice 2 effective methods&#xD;
             of contraception from the first dose of conditioning regimen through day +180. A woman&#xD;
             of reproductive capability is one who has not undergone a hysterectomy (removal of the&#xD;
             womb), has not had both ovaries removed, or has not been post-menopausal (stopped&#xD;
             menstrual periods) for more than 24 months in a row.&#xD;
&#xD;
          3. Male subjects who refuse to practice effective barrier contraception during the entire&#xD;
             study treatment period and through a minimum of 90 days after the last dose of study&#xD;
             drug, or completely abstain from heterosexual intercourse. This must be done even if&#xD;
             they are surgically sterilized (i.e., post-vasectomy).&#xD;
&#xD;
          4. Inability to provide informed consent.&#xD;
&#xD;
          5. Patient had myocardial infarction within 6 months prior to enrollment or has New York&#xD;
             Heart Association (NYHA) Class III or IV heart failure (see Appendix E), uncontrolled&#xD;
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence&#xD;
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any&#xD;
             ECG abnormality at screening must be documented by the investigator as not medically&#xD;
             relevant.&#xD;
&#xD;
          6. Known allergies to any of the components of the investigational treatment regimen.&#xD;
&#xD;
          7. Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study.&#xD;
&#xD;
          8. Participation in clinical trials with other investigational agents not included in&#xD;
             this trial, within 14 days of the start of this trial and throughout the duration of&#xD;
             this trial.&#xD;
&#xD;
          9. Prisoners&#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>Samer Al-Homsi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 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>Cyclophosphamide</mesh_term>
    <mesh_term>Abatacept</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to the PI. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>beginning 9 months and ending 36 months following article publication</ipd_time_frame>
    <ipd_access_criteria>Requests may be directed to the PI.</ipd_access_criteria>
  </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/NCT04503616
org study id: 20-00136
nct id: NCT04503616
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single arm, open label, optimal 2-stage Simon design phase Ib-II clinical trial.
      Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or
      second-degree haploidentical donor are eligible for the study if they meet the standard
      criteria defined in our institutional standard operation procedures (SOPs), meet all
      inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive
      non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by
      peripheral blood hematopoietic stem cells. Patients will receive cyclophosphamide, abatacept,
      and short-duration tacrolimus for GvHD prophylaxis.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Interventional, non-randomized open label, 2- stage optimal Simon design with interim futility analysis.
primary purpose: Prevention
masking: None (Open Label)
measure: Cumulative Incidence of Grade II-IV Acute GvHD by Day +120
time frame: 120 days
description: The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Overall Grades of Acute GvHD:
0 = none;
= mild;
= moderate;
= severe;
= life threatening
measure: Cumulative Incidence of Chronic GvHD
time frame: Day 365
description: The first day of chronic GvHD will be used to calculate the cumulative incidence of chronic GvHD. This endpoint will be evaluated through day +365 post-transplant.
measure: Cumulative Incidence of Primary Graft Failure
time frame: Day 45
description: Graft failure is defined as failure to achieve neutrophil engraftment by day +28 or lack of donor chimerism > 50% by day 45, not due to the underlying malignancy.
measure: Cumulative Incidence of Poor Graft Function
time frame: Day 28
description: Poor Graft Function defined by at least 2 of the following 3 criteria: Hemoglobin < 8 g/dL, ANC < 0.5 x 109/L, and platelets < 20 x 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks.
measure: Incidence of Secondary Graft Failure
time frame: Day 730
description: Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism < 5%.
measure: Number of Treatment-Related Deaths
time frame: Day 730
description: Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.
measure: Relapse Rate
time frame: Day 730
description: Evaluated to day +730 and defined as the percentage of patients in whom the disease for which transplant is performed becomes evident by methods of disease detection after the transplant.
measure: GvHD and Relapse-Free Survival (GRFS)
time frame: Day 730
description: Evaluated to day +730 and defined as the percentage of participants who are without reported grade III-IV acute GvHD, without chronic GvHD requiring systemic therapy, and have not experienced relapse or death.
measure: Overall Survival
time frame: Day 730
description: Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.
arm group label: HSCT Patients
arm group type: Experimental
description: Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.
intervention type: Drug
intervention name: Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
description: Cyclophosphamide 50 mg/kg IV over 2 hours on Day +3 and +4 Abatacept 10 mg/kg IV on days +5, +14, and +28 Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on day +5. May switch to oral when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Treatment is discontinued on day +60 after a 4 week-taper
arm group label: HSCT Patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Samer Al-Homsi, MD
role: Principal Investigator
affiliation: NYU Langone Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Graft vs Host Disease
mesh term: Cyclophosphamide
mesh term: Abatacept
mesh term: Tacrolimus
sharing ipd: Yes
ipd description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to the PI. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: beginning 9 months and ending 36 months following article publication
ipd access criteria: Requests may be directed to the PI.