<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/NCT02988466</url>
  </required_header>
  <id_info>
    <org_study_id>2016LS092</org_study_id>
    <secondary_id>MT2016-15</secondary_id>
    <nct_id>NCT02988466</nct_id>
  </id_info>
  <brief_title>Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT</brief_title>
  <official_title>Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single institution phase II study of a reduced intensity conditioning (RIC)&#xD;
      followed by a haploidentical hematopoietic cell transplant (haplo-HCT) in persons with&#xD;
      diagnosis of hematologic malignancy. Conditioning will consists of fludarabine,&#xD;
      cyclophosphamide, melphalan and total body irradiation (TBI) preparative regimen with a&#xD;
      melphalan dose reduction for patients ≥55 years old and those with HCT Comorbidity Index (CI)&#xD;
      &gt;3. This study uses a two-stage phase II design with accrual goal of 84 patients, using 28&#xD;
      patients separately for arms A, C and D&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 24, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Actual">May 2, 2023</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>Disease-free survival (DFS)</measure>
    <time_frame>1 year</time_frame>
    <description>estimate disease-free survival (DFS) at 1 year post-transplant</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of grade II-IV and grade III-IV acute graft versus-host-disease (GVHD)</measure>
    <time_frame>day 100</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment related mortality (TRM)</measure>
    <time_frame>6 month, 1 and 2 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse incidence</measure>
    <time_frame>1 and 2 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious fungal and viral infection</measure>
    <time_frame>at day 100 and 1 year</time_frame>
    <description>post-HCT</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Hematologic Malignancies</condition>
  <arm_group>
    <arm_group_label>Arm A: Haplo-HCT &lt;55 years old</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients &lt;55 years old with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CLOSED Arm B: Haplo-HCT ≥55 years old</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients ≥55 years old or younger with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and &lt; 65yo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2 aged ≥55 and &lt; 65 years old.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients patients ≥65 and ≤75 years old OR any age group with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Haplo HCT &lt;55 years old</intervention_name>
    <description>Fludarabine (Flu)&#xD;
Cyclophosphamide (Cy)&#xD;
Melphalan (Mel)&#xD;
Total body irradiation (TBI)&#xD;
Non-T-cell depleted donor bone marrow stem cell infusion Day 0</description>
    <arm_group_label>Arm A: Haplo-HCT &lt;55 years old</arm_group_label>
    <other_name>HLA-haploidentical related hematopoietic cells transplant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Haplo HCT ≥55 years old</intervention_name>
    <description>Fludarabine (Flu)&#xD;
Cyclophosphamide (Cy)&#xD;
Melphalan (Mel): Dose reduction by 30%&#xD;
Total body irradiation (TBI)&#xD;
Non-T-cell depleted donor bone marrow stem cell infusion</description>
    <arm_group_label>CLOSED Arm B: Haplo-HCT ≥55 years old</arm_group_label>
    <other_name>HLA-haploidentical related hematopoietic cells transplant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GVHD Prophylaxis</intervention_name>
    <description>Cyclophosphamide (Cy)&#xD;
Tacrolimus (Tac)&#xD;
Mycophenolate mofetil (MMF)</description>
    <arm_group_label>Arm A: Haplo-HCT &lt;55 years old</arm_group_label>
    <arm_group_label>Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and &lt; 65yo</arm_group_label>
    <arm_group_label>Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3</arm_group_label>
    <arm_group_label>CLOSED Arm B: Haplo-HCT ≥55 years old</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Haplo HCT ≥55 and &lt; 65 years old</intervention_name>
    <description>Fludarabine (Flu)&#xD;
Cyclophosphamide (Cy)&#xD;
Melphalan (Mel)&#xD;
Total body irradiation (TBI)&#xD;
non-T-cell depleted donor bone marrow stem cells</description>
    <arm_group_label>Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and &lt; 65yo</arm_group_label>
    <other_name>HLA-haploidentical related hematopoietic cells transplant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Haplo HCT ≥65 and ≤75 years old</intervention_name>
    <description>Fludarabine (Flu)&#xD;
Cyclophosphamide (Cy)&#xD;
Total body irradiation (TBI)</description>
    <arm_group_label>Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3</arm_group_label>
    <other_name>HLA-haploidentical related hematopoietic cells transplant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Karnofsky performance status of ≥70% or Lansky play score ≥ 70%&#xD;
&#xD;
          -  A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches&#xD;
&#xD;
          -  The donor and recipient must be HLA identical for at least one haplotype (using high&#xD;
             resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and&#xD;
             HLA-DRB1.&#xD;
&#xD;
          -  Adequate liver and renal function&#xD;
&#xD;
          -  Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left&#xD;
             ventricular ejection fraction ≥ 40%&#xD;
&#xD;
          -  Diffusion capacity corrected (DLCOcorr) &gt; 40% predicted, and absence of O2&#xD;
             requirements&#xD;
&#xD;
          -  &gt; 6 months after prior autologous transplant (if applicable)&#xD;
&#xD;
          -  Agrees to use contraception during study treatment&#xD;
&#xD;
          -  Voluntary written consent (adult or parent/guardian with presentation of the minor&#xD;
             information sheet, if appropriate)&#xD;
&#xD;
          -  Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be&#xD;
             evaluated by Infectious Disease (ID) and a HIV management plan establish prior to&#xD;
             transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt; 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Current active and uncontrolled serious infection&#xD;
&#xD;
          -  Acute leukemia in morphologic relapse/persistent disease defined as &gt; 5% blasts in&#xD;
             normocellular bone marrow OR any % blasts if blasts have unique morphologic markers&#xD;
             (e.g. Auer rods).&#xD;
&#xD;
          -  CML in blast crisis&#xD;
&#xD;
          -  Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on&#xD;
             salvage therapy.&#xD;
&#xD;
          -  stable non-bulky disease is acceptable.&#xD;
&#xD;
          -  Active central nervous system malignancy&#xD;
&#xD;
        Criteria For Donor Selection:&#xD;
&#xD;
          -  Donors must be HLA-haploidentical relatives of the patient, defined as having a shared&#xD;
             HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.&#xD;
&#xD;
          -  Eligible donors (14-70 years old) include biological children, siblings or half&#xD;
             siblings, or parents, able and willing to undergo bone marrow harvesting.&#xD;
&#xD;
          -  For donors &lt;18 years, the maximum recipient weight (actual body weight) should not&#xD;
             exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow&#xD;
             product volume should be limited to 20 ml/kg donor weight for donors &lt;18 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Najla El Jurdi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Masonic Cancer Center, University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Masonic Cancer Center at 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>May 2023</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Leukemias</keyword>
  <keyword>Acute myeloid leukemia (AML)</keyword>
  <keyword>Acute lymphoblastic leukemia (ALL)/lymphoma</keyword>
  <keyword>Biphenotypic/Undifferentiated/Prolymphocytic Leukemias</keyword>
  <keyword>Myelodysplastic syndrome</keyword>
  <keyword>Chronic myelogenous leukemia</keyword>
  <keyword>Minimal Residual Disease (MRD) positive leukemia</keyword>
  <keyword>Leukemia or Myelodysplastic Syndromes (MDS) in aplasia</keyword>
  <keyword>Myeloproliferative neoplasms/myelofibrosis</keyword>
  <keyword>Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma</keyword>
  <keyword>Burkitt's lymphoma</keyword>
  <keyword>Relapsed T-cell lymphoma</keyword>
  <keyword>Natural Killer cell malignancies</keyword>
  <keyword>Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma</keyword>
  <keyword>Lymphoplasmacytic lymphoma</keyword>
  <keyword>Relapsed multiple myeloma</keyword>
  <keyword>Bone marrow failure syndromes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_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/NCT02988466
org study id: 2016LS092
secondary id: MT2016-15
nct id: NCT02988466
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single institution phase II study of a reduced intensity conditioning (RIC)
      followed by a haploidentical hematopoietic cell transplant (haplo-HCT) in persons with
      diagnosis of hematologic malignancy. Conditioning will consists of fludarabine,
      cyclophosphamide, melphalan and total body irradiation (TBI) preparative regimen with a
      melphalan dose reduction for patients ≥55 years old and those with HCT Comorbidity Index (CI)
      >3. This study uses a two-stage phase II design with accrual goal of 84 patients, using 28
      patients separately for arms A, C and D
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease-free survival (DFS)
time frame: 1 year
description: estimate disease-free survival (DFS) at 1 year post-transplant
measure: Incidence of grade II-IV and grade III-IV acute graft versus-host-disease (GVHD)
time frame: day 100
measure: Treatment related mortality (TRM)
time frame: 6 month, 1 and 2 year
measure: Relapse incidence
time frame: 1 and 2 year
measure: Incidence of serious fungal and viral infection
time frame: at day 100 and 1 year
description: post-HCT
arm group label: Arm A: Haplo-HCT <55 years old
arm group type: Experimental
description: Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients <55 years old with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2
arm group label: CLOSED Arm B: Haplo-HCT ≥55 years old
arm group type: Experimental
description: Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients ≥55 years old or younger with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
arm group label: Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo
arm group type: Experimental
description: Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2 aged ≥55 and < 65 years old.
arm group label: Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3
arm group type: Experimental
description: Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients patients ≥65 and ≤75 years old OR any age group with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
intervention type: Biological
intervention name: Haplo HCT <55 years old
description: Fludarabine (Flu)
Cyclophosphamide (Cy)
Melphalan (Mel)
Total body irradiation (TBI)
Non-T-cell depleted donor bone marrow stem cell infusion Day 0
arm group label: Arm A: Haplo-HCT <55 years old
other name: HLA-haploidentical related hematopoietic cells transplant
intervention type: Biological
intervention name: Haplo HCT ≥55 years old
description: Fludarabine (Flu)
Cyclophosphamide (Cy)
Melphalan (Mel): Dose reduction by 30%
Total body irradiation (TBI)
Non-T-cell depleted donor bone marrow stem cell infusion
arm group label: CLOSED Arm B: Haplo-HCT ≥55 years old
other name: HLA-haploidentical related hematopoietic cells transplant
intervention type: Drug
intervention name: GVHD Prophylaxis
description: Cyclophosphamide (Cy)
Tacrolimus (Tac)
Mycophenolate mofetil (MMF)
arm group label: Arm A: Haplo-HCT <55 years old
arm group label: Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo
arm group label: Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3
arm group label: CLOSED Arm B: Haplo-HCT ≥55 years old
intervention type: Biological
intervention name: Haplo HCT ≥55 and < 65 years old
description: Fludarabine (Flu)
Cyclophosphamide (Cy)
Melphalan (Mel)
Total body irradiation (TBI)
non-T-cell depleted donor bone marrow stem cells
arm group label: Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo
other name: HLA-haploidentical related hematopoietic cells transplant
intervention type: Biological
intervention name: Haplo HCT ≥65 and ≤75 years old
description: Fludarabine (Flu)
Cyclophosphamide (Cy)
Total body irradiation (TBI)
arm group label: Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3
other name: HLA-haploidentical related hematopoietic cells transplant
criteria: 
gender: All
minimum age: N/A
maximum age: 75 Years
healthy volunteers: No
last name: Najla El Jurdi, MD
role: Principal Investigator
affiliation: Masonic Cancer Center, University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Hematologic Neoplasms