<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/NCT03267186</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-38934</org_study_id>
    <secondary_id>NCI-2017-00125</secondary_id>
    <secondary_id>IRB-38934</secondary_id>
    <secondary_id>BMT302</secondary_id>
    <nct_id>NCT03267186</nct_id>
  </id_info>
  <brief_title>Ibrutinib in Preventing Acute Leukemia in Patients After Reduced-Intensity Conditioning and Stem Cell Transplant</brief_title>
  <official_title>A Phase 2 Study of Ibrutinib Maintenance After Reduced-Intensity Conditioning and Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Andrew Rezvani</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pharmacyclics LLC.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</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 phase II trial studies how well ibrutinib works in preventing acute leukemia in patients&#xD;
      after reduced-intensity conditioning and stem cell transplant. Ibrutinib may stop the growth&#xD;
      of tumor cells by blocking some of the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To reduce the incidence of relapse at 18 months after reduced-intensity conditioning (RIC)&#xD;
      and allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML),&#xD;
      acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) in blast crisis from a&#xD;
      historical baseline of 45% to 25%, using ibrutinib maintenance therapy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To study the incidence and severity of post-transplant complications in subjects receiving&#xD;
      ibrutinib maintenance after allogeneic HCT.&#xD;
&#xD;
      II. To study the incidence of infectious complications in subjects receiving maintenance&#xD;
      ibrutinib after allogeneic HCT.&#xD;
&#xD;
      III. To study the impact of ibrutinib maintenance on minimal residual disease after RIC and&#xD;
      allogeneic HCT.&#xD;
&#xD;
      IV. To study the impact of maintenance ibrutinib on immune reconstitution and alloreactivity&#xD;
      after allogeneic HCT, specifically on Th1/ Th2 polarization, T follicular cell number, T and&#xD;
      B cell repertoire, serum immunoglobulin levels, and alloantibody formation.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib orally (PO) once daily&#xD;
      (QD) for up to 18 months post-transplant in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 12, 2017</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</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>Number of Participants With Relapsed Leukemia</measure>
    <time_frame>Up to 18 months</time_frame>
    <description>Relapsed leukemia is defined as &gt; 5% leukemic blasts detected in bone marrow or peripheral blood. Participants were also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have &lt; 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)</measure>
    <time_frame>At 180 days</time_frame>
    <description>Acute GVHD grades II-IV and III-IV was evaluated according to the following criteria.&#xD;
Stage of Acute GvHD was assessed as follows.&#xD;
Stage 1: Skin: rash &lt; 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea &gt;500 mL/day or upper-gut symptoms with positive histology&#xD;
Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea &gt;1000 mL/day.&#xD;
Stage 3: Skin: rash &gt; 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea &gt; 1500 mL/day.&#xD;
Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin &gt; 15 mg/dL. Gut: diarrhea &gt; 2500 mL/day or severe abdominal pain with or without ileus&#xD;
Grade of Acute GvHD was determined as follows.&#xD;
Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage&#xD;
Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut&#xD;
Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut&#xD;
Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Chronic GVHD</measure>
    <time_frame>At 18 months</time_frame>
    <description>Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Negative for Detectable Minimal Residual Disease</measure>
    <time_frame>day +90, day +180, 1 year, 1.5 years</time_frame>
    <description>Detectable minimal residual disease was assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease was considered present if &gt; 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Acute Biphenotypic Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Hematopoietic Cell Transplantation Recipient</condition>
  <arm_group>
    <arm_group_label>Prevention (ibrutinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Prevention (ibrutinib)</arm_group_label>
    <other_name>BTK Inhibitor PCI-32765</other_name>
    <other_name>CRA-032765</other_name>
    <other_name>Imbruvica</other_name>
    <other_name>PCI-32765</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Prevention (ibrutinib)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  INCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT)&#xD;
&#xD;
          -  Diagnosis of acute myeloid leukemia (AML), acute biphenotypic leukemia, or acute&#xD;
             lymphoblastic leukemia (ALL); CML transformed to blast crisis is eligible&#xD;
&#xD;
          -  Planned allogeneic HCT using fludarabine phosphate (FLU)/melphalan hydrochloride (MEL)&#xD;
             or FLU/busulfan (BU) conditioning&#xD;
&#xD;
          -  Planned graft versus host disease (GVHD) prophylaxis consisting of tacrolimus&#xD;
             (TAC)/methotrexate (MTX) or TAC/sirolimus (SRL)&#xD;
&#xD;
          -  Human leukocyte antigen (HLA) identical sibling donor, HLA matched unrelated donor, or&#xD;
             donor mismatched at 1 HLA allele or antigen&#xD;
&#xD;
          -  Less than or equal to 5% blasts on bone marrow examination within 60 days of starting&#xD;
             conditioning&#xD;
&#xD;
          -  Age &gt;= 18 years and =&lt; 70 years&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
          -  Subjects will be eligible if their planned conditioning regimen for allogeneic HCT&#xD;
             consists of one of the two following standard reduced intensity conditioning regimens:&#xD;
&#xD;
               -  FLU/MEL: fludarabine phosphate (fludarabine) 120 to 180 mg/m^2; melphalan&#xD;
                  hydrochloride (melphalan) =&lt; 150 mg/m^2&#xD;
&#xD;
               -  FLU/BU: fludarabine 120 to 180 mg/m^2; busulfan =&lt; 8 mg/kg orally or =&lt; 6.4 mg/kg&#xD;
                  intravenously&#xD;
&#xD;
          -  Subjects will be eligible if their planned post grafting immunosuppression consists of&#xD;
             one of the two following regimens:&#xD;
&#xD;
               -  TAC/MTX: tacrolimus (oral or intravenous) and intravenous methotrexate&#xD;
                  administered according to institutional standard practice.&#xD;
&#xD;
               -  TAC/SRL: tacrolimus (oral or intravenous) and oral sirolimus, administered&#xD;
                  according to institutional standards of care&#xD;
&#xD;
          -  INCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION)&#xD;
&#xD;
          -  Age &gt;= 18 years&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt; 0.75 x 10^9/L&#xD;
&#xD;
          -  Platelet count &gt; 50 x 10^9/L&#xD;
&#xD;
          -  Hemoglobin &gt; 8.0 g/dL without transfusion or growth factor support for at least 7 days&#xD;
             prior to screening (with the exception of pegylated granulocyte-colony stimulating&#xD;
             factor [G-CSF] and darbopoietin, which require at least 14 days of abstinence prior to&#xD;
             screening)&#xD;
&#xD;
          -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =&lt; 3.0 x&#xD;
             upper limit of normal&#xD;
&#xD;
          -  Estimated creatinine clearance &gt;= 30 mL/min via Cockroft-Gault formula&#xD;
&#xD;
          -  Bilirubin =&lt; 1.5 x upper limit of normal (unless elevated bilirubin is due to&#xD;
             Gilbert's syndrome or of non-hepatic origin)&#xD;
&#xD;
          -  Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin&#xD;
             time (PTT) (activated partial thromboplastin time [aPTT]) =&lt; 1.5 x upper limit of&#xD;
             normal&#xD;
&#xD;
          -  Female subjects who are of non-reproductive potential (ie, post-menopausal by history&#xD;
             - no menses for &gt;= 1 year; OR history of hysterectomy; OR history of bilateral tubal&#xD;
             ligation; OR history of bilateral oophorectomy); female subjects of childbearing&#xD;
             potential must have a negative serum pregnancy test upon screening&#xD;
&#xD;
          -  Male and female subjects who agree to use both a highly effective method of birth&#xD;
             control (eg, implants, injectables, combined oral contraceptives, some intrauterine&#xD;
             devices [IUDs], sexual abstinence, or sterilized partner) and a barrier method (eg,&#xD;
             condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after&#xD;
             the last dose of study drug for females and 90 days after the last dose of the study&#xD;
             drug for males&#xD;
&#xD;
          -  Between day +60 and day +90 after allogeneic HCT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active involvement of the central&#xD;
             nervous system with malignancy (previous central nervous system [CNS] involvement is&#xD;
             allowed if clearance of CNS disease has been documented prior to enrollment)&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Pregnant or breastfeeding&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Karnofsky performance status &lt; 60%&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active leukemia (&gt; 5% leukemic&#xD;
             blasts in peripheral blood or bone marrow)&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Non-hematologic malignancy with a&#xD;
             life expectancy of &lt; 5 years&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known history of human&#xD;
             immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus&#xD;
             (HBV) infection; subjects who are positive for hepatitis B core antibody or hepatitis&#xD;
             B surface antigen must have a negative polymerase chain reaction (PCR) result before&#xD;
             enrollment; those who are PCR positive will be excluded&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known bleeding disorders (eg, von&#xD;
             Willebrand's disease) or hemophilia&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): History of other malignancies,&#xD;
             except:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease present&#xD;
                  for &gt;= 3 years before the first dose of study drug and felt to be at low risk for&#xD;
                  recurrence by treating physician&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease Adequately treated carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Active and uncontrolled acute&#xD;
             GVHD grades III or IV&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Use of secondary therapy for&#xD;
             acute GVHD at any time (defined as any systemic therapy intended to treat acute GVHD&#xD;
             besides corticosteroids)&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requirement for&#xD;
             anticoagulation with warfarin or other vitamin K antagonists (concomitant use of other&#xD;
             anticoagulants is permitted)&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Relapsed leukemia (&gt; 5%&#xD;
             leukemic blasts in peripheral blood or bone marrow after allogeneic HCT)&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Karnofsky performance status &lt;&#xD;
             60%&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Chemotherapy =&lt; 21 days prior&#xD;
             to first administration of study treatment and/or monoclonal antibody =&lt; 6 weeks prior&#xD;
             to first administration of study treatment&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Vaccinated with live,&#xD;
             attenuated vaccines within 4 weeks of first dose of study drug&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Currently active, clinically&#xD;
             significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4&#xD;
             congestive heart failure as defined by the New York Heart Association Functional&#xD;
             Classification; or a history of myocardial infarction, unstable angina, or acute&#xD;
             coronary syndrome within 6 months prior to randomization&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): History of stroke or&#xD;
             intracranial hemorrhage within 6 months prior to screening&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any life threatening illness,&#xD;
             medical condition, or organ system dysfunction that, in the investigator's opinion,&#xD;
             could compromise the subject's safety or put the study outcomes at undue risk&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Major surgery within 4 weeks&#xD;
             of first dose of study drug&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any uncontrolled active&#xD;
             systemic infection&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unresolved toxicities from&#xD;
             prior anti cancer therapy, defined as having not resolved to Common Terminology&#xD;
             Criteria for Adverse Event (CTCAE, version 4), grade =&lt; 1, or to the levels dictated&#xD;
             in the inclusion/exclusion criteria with the exception of alopecia&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unable to swallow capsules or&#xD;
             malabsorption syndrome, disease significantly affecting gastrointestinal function, or&#xD;
             resection of the stomach or small bowel, symptomatic inflammatory bowel disease or&#xD;
             ulcerative colitis, or partial or complete bowel obstruction&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requires treatment with a&#xD;
             strong cytochrome P450 (CYP) 3A4/5 inhibitor&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unwilling or unable to&#xD;
             participate in all required study evaluations and procedures&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unable to understand the&#xD;
             purpose and risks of the study and to provide a signed and dated informed consent form&#xD;
             (ICF) and authorization to use protected health information (in accordance with&#xD;
             national and local subject privacy regulations)&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Currently active, clinically&#xD;
             significant hepatic impairment (Child-Pugh class B or C)&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Lactating or pregnant&#xD;
&#xD;
          -  EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Uncontrolled cardiac&#xD;
             arrhythmias&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Rezvani</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University, School of Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.</citation>
    <PMID>25529383</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <results_first_submitted>May 11, 2023</results_first_submitted>
  <results_first_submitted_qc>July 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2023</results_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Andrew Rezvani</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Biphenotypic, Acute</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03267186/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <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>December 8, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03267186/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Prevention (Ibrutinib)</title>
          <description>Beginning 60-90 days after allogeneic hematopoietic cell transplantation (HCT), patients receive ibrutinib orally (PO) once daily (QD) for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Prevention (Ibrutinib)</title>
          <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>50-59</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Acute leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acute myeloid leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Relapsed Leukemia</title>
        <description>Relapsed leukemia is defined as &gt; 5% leukemic blasts detected in bone marrow or peripheral blood. Participants were also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have &lt; 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.</description>
        <time_frame>Up to 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prevention (Ibrutinib)</title>
            <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Relapsed Leukemia</title>
          <description>Relapsed leukemia is defined as &gt; 5% leukemic blasts detected in bone marrow or peripheral blood. Participants were also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have &lt; 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Relapsed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not relapsed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)</title>
        <description>Acute GVHD grades II-IV and III-IV was evaluated according to the following criteria.&#xD;
Stage of Acute GvHD was assessed as follows.&#xD;
Stage 1: Skin: rash &lt; 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea &gt;500 mL/day or upper-gut symptoms with positive histology&#xD;
Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea &gt;1000 mL/day.&#xD;
Stage 3: Skin: rash &gt; 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea &gt; 1500 mL/day.&#xD;
Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin &gt; 15 mg/dL. Gut: diarrhea &gt; 2500 mL/day or severe abdominal pain with or without ileus&#xD;
Grade of Acute GvHD was determined as follows.&#xD;
Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage&#xD;
Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut&#xD;
Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut&#xD;
Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage</description>
        <time_frame>At 180 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prevention (Ibrutinib)</title>
            <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)</title>
          <description>Acute GVHD grades II-IV and III-IV was evaluated according to the following criteria.&#xD;
Stage of Acute GvHD was assessed as follows.&#xD;
Stage 1: Skin: rash &lt; 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea &gt;500 mL/day or upper-gut symptoms with positive histology&#xD;
Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea &gt;1000 mL/day.&#xD;
Stage 3: Skin: rash &gt; 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea &gt; 1500 mL/day.&#xD;
Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin &gt; 15 mg/dL. Gut: diarrhea &gt; 2500 mL/day or severe abdominal pain with or without ileus&#xD;
Grade of Acute GvHD was determined as follows.&#xD;
Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage&#xD;
Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut&#xD;
Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut&#xD;
Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Chronic GVHD</title>
        <description>Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.</description>
        <time_frame>At 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prevention (Ibrutinib)</title>
            <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Chronic GVHD</title>
          <description>Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Negative for Detectable Minimal Residual Disease</title>
        <description>Detectable minimal residual disease was assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease was considered present if &gt; 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.</description>
        <time_frame>day +90, day +180, 1 year, 1.5 years</time_frame>
        <population>Participants who had minimal residual disease testing at the respective time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Prevention (Ibrutinib)</title>
            <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Negative for Detectable Minimal Residual Disease</title>
          <description>Detectable minimal residual disease was assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease was considered present if &gt; 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.</description>
          <population>Participants who had minimal residual disease testing at the respective time point.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>day +90</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>day +180</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1.5 years</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Prevention (Ibrutinib)</title>
          <description>Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oral Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Imbalance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Edema, bilateral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Leg Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Bilateral Hand Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of breath (dyspnea)</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Facial hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Itchy Skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study did not enroll the planned number of participants and did not achieve statistical power.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Andrew R. Rezvani, MD</name_or_title>
      <organization>Stanford University</organization>
      <phone>650-725-4077</phone>
      <email>arezvani@stanford.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03267186
org study id: IRB-38934
secondary id: NCI-2017-00125
secondary id: IRB-38934
secondary id: BMT302
nct id: NCT03267186
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well ibrutinib works in preventing acute leukemia in patients
      after reduced-intensity conditioning and stem cell transplant. Ibrutinib may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:

      I. To reduce the incidence of relapse at 18 months after reduced-intensity conditioning (RIC)
      and allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML),
      acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) in blast crisis from a
      historical baseline of 45% to 25%, using ibrutinib maintenance therapy.

      SECONDARY OBJECTIVES:

      I. To study the incidence and severity of post-transplant complications in subjects receiving
      ibrutinib maintenance after allogeneic HCT.

      II. To study the incidence of infectious complications in subjects receiving maintenance
      ibrutinib after allogeneic HCT.

      III. To study the impact of ibrutinib maintenance on minimal residual disease after RIC and
      allogeneic HCT.

      IV. To study the impact of maintenance ibrutinib on immune reconstitution and alloreactivity
      after allogeneic HCT, specifically on Th1/ Th2 polarization, T follicular cell number, T and
      B cell repertoire, serum immunoglobulin levels, and alloantibody formation.

      OUTLINE:

      Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib orally (PO) once daily
      (QD) for up to 18 months post-transplant in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Relapsed Leukemia
time frame: Up to 18 months
description: Relapsed leukemia is defined as > 5% leukemic blasts detected in bone marrow or peripheral blood. Participants were also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have < 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.
measure: Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)
time frame: At 180 days
description: Acute GVHD grades II-IV and III-IV was evaluated according to the following criteria.
Stage of Acute GvHD was assessed as follows.
Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea >500 mL/day or upper-gut symptoms with positive histology
Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea >1000 mL/day.
Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: diarrhea > 2500 mL/day or severe abdominal pain with or without ileus
Grade of Acute GvHD was determined as follows.
Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
measure: Number of Participants With Chronic GVHD
time frame: At 18 months
description: Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.
measure: Number of Participants Negative for Detectable Minimal Residual Disease
time frame: day +90, day +180, 1 year, 1.5 years
description: Detectable minimal residual disease was assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease was considered present if > 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.
arm group label: Prevention (ibrutinib)
arm group type: Experimental
description: Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Ibrutinib
description: Given PO
arm group label: Prevention (ibrutinib)
other name: BTK Inhibitor PCI-32765
other name: CRA-032765
other name: Imbruvica
other name: PCI-32765
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Prevention (ibrutinib)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Andrew Rezvani
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
citation: Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.
PMID: 25529383
responsible party type: Sponsor-Investigator
investigator affiliation: Stanford University
investigator full name: Andrew Rezvani
investigator title: Associate Professor of Medicine
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Biphenotypic, Acute
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study did not enroll the planned number of participants and did not achieve statistical power.
point of contact: 