<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/NCT02997761</url>
  </required_header>
  <id_info>
    <org_study_id>945122</org_study_id>
    <secondary_id>UCDCC#266</secondary_id>
    <secondary_id>UCDCC#266</secondary_id>
    <secondary_id>P30CA093373</secondary_id>
    <secondary_id>NCI-2016-01882</secondary_id>
    <nct_id>NCT02997761</nct_id>
  </id_info>
  <brief_title>Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia</brief_title>
  <official_title>A Phase 2 Study of Ibrutinib and Blinatumomab in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brian Jonas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pharmacyclics LLC.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Davis</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 and blinatumomab work in treating patients&#xD;
      with B acute lymphoblastic leukemia that has come back or is not responding to treatment.&#xD;
      Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell&#xD;
      growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer&#xD;
      cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating&#xD;
      patients with relapsed or refractory B acute lymphoblastic leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or&#xD;
      refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with&#xD;
      relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR&#xD;
      with incomplete count recovery [CRi]), relapse free survival (RFS), overall survival (OS),&#xD;
      minimal residual disease (MRD) response, proportion of patients bridged to allogeneic&#xD;
      hematopoietic cell transplant (allo-HCT), and toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 27, 2017</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>Rate of CR</measure>
    <time_frame>Up to 91 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events graded according to the National Cancer Institute CTCAE v4.03</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRD response</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR defined as CR plus CRi assessed by disease-specific response criteria</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>From the time of first study drug administration until the date of progression or death from any cause, assessed for up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RFS</measure>
    <time_frame>Time from CR/CRi until the date of progression or death from any cause, assessed for up to 6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Adult B Acute Lymphoblastic Leukemia</condition>
  <condition>Philadelphia Chromosome Positive</condition>
  <arm_group>
    <arm_group_label>Treatment (ibrutinib, blinatumomab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blinatumomab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ibrutinib, blinatumomab)</arm_group_label>
    <other_name>Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody</other_name>
    <other_name>Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103</other_name>
    <other_name>Blincyto</other_name>
    <other_name>MEDI-538</other_name>
    <other_name>MT-103</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ibrutinib, blinatumomab)</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed diagnosis of relapsed or refractory B-cell acute&#xD;
             lymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts or&#xD;
             biopsy-proven extramedullary site measurable by computed tomography (CT) or positron&#xD;
             emission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALL&#xD;
             patients must have failed treatment with at least one second generation tyrosine&#xD;
             kinase inhibitor; prior allo-HCT is allowed&#xD;
&#xD;
          -  No hematologic parameters for inclusion; transfusion-dependent patients are eligible&#xD;
             and platelet counts should be maintained greater than 10,000/mm^3 throughout cycles 1&#xD;
             and 2&#xD;
&#xD;
          -  Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless bilirubin&#xD;
             rise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)&#xD;
&#xD;
          -  Serum aspartate transaminase (aspartate aminotransferase [AST]) or alanine&#xD;
             transaminase (alanine aminotransferase [ALT]) less than or equal to 3 x ULN (unless&#xD;
             due to B-ALL)&#xD;
&#xD;
          -  Estimated creatinine clearance greater than or equal to 30 ml/min (Cockcroft-Gault) or&#xD;
             serum creatinine less than or equal to 2 x ULN&#xD;
&#xD;
          -  Prothrombin time (PT)/international normalized ratio (INR) =&lt; 1.5 x ULN and partial&#xD;
             thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) =&lt; 1.5 x ULN&#xD;
             (unless B-ALL related)&#xD;
&#xD;
          -  Karnofsky performance status (KPS) performance status of 60% or greater&#xD;
&#xD;
          -  Ability to understand and willingness to sign an informed consent form&#xD;
&#xD;
          -  Ability to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
          -  Female subjects who are of non-reproductive potential (i.e., post-menopausal by&#xD;
             history - no menses for &gt;= 1 year; OR history of hysterectomy; OR history of bilateral&#xD;
             tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing&#xD;
             potential must have a negative serum or urine pregnancy test within 72 hours prior to&#xD;
             the first study drug administration&#xD;
&#xD;
          -  Male and female subjects who agree to use both a highly effective methods of birth&#xD;
             control (e.g., condoms, implants, injectables, combined oral contraceptives, some&#xD;
             intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier&#xD;
             method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for&#xD;
             90 days after the last dose of study drug&#xD;
&#xD;
          -  Eligibility of patients receiving any medications or substances known to affect or&#xD;
             with the potential to affect the activity or pharmacokinetics of ibrutinib or&#xD;
             blinatumomab will be determined following review of their case by the investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt's leukemia/lymphoma&#xD;
&#xD;
          -  Patients with current evidence of active central nervous system (CNS) leukemia&#xD;
&#xD;
          -  History of treatment with ibrutinib or blinatumomab&#xD;
&#xD;
          -  Investigational therapy, chemotherapy, immunotherapy, radiotherapy, or systemic graft&#xD;
             versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is&#xD;
             shorter); steroids, hydroxyurea and/or leukapheresis are allowed to control blast&#xD;
             count prior to the first dose of study drug&#xD;
&#xD;
          -  Prior allo-HCT less than three months from the time of enrollment&#xD;
&#xD;
          -  Any active acute GVHD or chronic GVHD greater than grade 1&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to ibrutinib and blinatumomab or other agents used in this study&#xD;
&#xD;
          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug&#xD;
&#xD;
          -  Recent culture-documented infection requiring intravenous antimicrobials that was&#xD;
             completed =&lt; 7 days before the first dose of study drug or any uncontrolled active&#xD;
             systemic infection; fever of unknown origin is not an exclusion criterion, as this may&#xD;
             be disease-related&#xD;
&#xD;
          -  Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved&#xD;
             to Common Terminology Criteria for Adverse Event (CTCAE, version [v]4.03), grade =&lt; 2,&#xD;
             or to the levels dictated in the inclusion/exclusion criteria with the exception of&#xD;
             alopecia&#xD;
&#xD;
          -  Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment&#xD;
&#xD;
          -  Active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or&#xD;
             hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody,&#xD;
             hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase&#xD;
             chain reaction (PCR) result before enrollment; those who are PCR positive will be&#xD;
             excluded; subjects with HIV must have a CD4 count at or above the institutional lower&#xD;
             limit of normal and not taking prohibited CYP3A strong inhibitors&#xD;
&#xD;
          -  Major surgery within 4 weeks of first dose of study drug&#xD;
&#xD;
          -  Any life-threatening illness, medical condition, or organ system dysfunction,&#xD;
             including but not limited to, ongoing or active infection, symptomatic congestive&#xD;
             heart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmune&#xD;
             disorder, or psychiatric illness/social situations that, in the investigator's&#xD;
             opinion, could compromise the subject's safety or put the study outcomes at undue&#xD;
             risk; currently active, clinically significant cardiovascular disease, such as&#xD;
             uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New&#xD;
             York Heart Association Functional Classification; or a history of myocardial&#xD;
             infarction, unstable angina, or acute coronary syndrome within 6 months prior to&#xD;
             enrollment&#xD;
&#xD;
          -  History of other malignancies, except for malignancy surgically resected (or treated&#xD;
             with other modalities) with curative intent, adequately treated in situ carcinoma of&#xD;
             the breast or cervix uteri, basal cell carcinoma of the skin or localized squamous&#xD;
             cell carcinoma of the skin; malignancy treated with curative intent with no known&#xD;
             active disease present for &gt;= 3 years&#xD;
&#xD;
          -  Concomitant use of warfarin or other Vitamin K antagonists&#xD;
&#xD;
          -  Subjects who received a strong cytochrome P 450 3A (CYP3A) inhibitor within 7 days&#xD;
             prior to the first dose of ibrutinib or subjects who require continuous treatment with&#xD;
             a strong CYP3A inhibitor&#xD;
&#xD;
          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C&#xD;
             according to the Child Pugh classification&#xD;
&#xD;
          -  Breastfeeding or pregnant&#xD;
&#xD;
          -  Participation in clinical trials with other investigational agents not included in&#xD;
             this trial throughout the duration of this trial&#xD;
&#xD;
          -  Unwilling or unable to participate in all required study evaluations and procedures or&#xD;
             unable to understand the purpose and risks of the study and to provide a signed and&#xD;
             dated informed consent form (ICF) and authorization to use protected health&#xD;
             information (in accordance with national and local subject privacy regulations)&#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>Brian Jonas</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brian A. Jonas</last_name>
      <phone>916-734-3772</phone>
      <email>bajonas@ucdavis.edu</email>
    </contact>
    <investigator>
      <last_name>Brian A. Jonas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>February 2, 2023</last_update_submitted>
  <last_update_submitted_qc>February 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Davis</investigator_affiliation>
    <investigator_full_name>Brian Jonas</investigator_full_name>
    <investigator_title>Principal Investigator</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, Lymphoid</mesh_term>
    <mesh_term>Philadelphia Chromosome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Blinatumomab</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Muromonab-CD3</mesh_term>
    <mesh_term>Antibodies, Bispecific</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02997761
org study id: 945122
secondary id: UCDCC#266
secondary id: UCDCC#266
secondary id: P30CA093373
secondary id: NCI-2016-01882
nct id: NCT02997761
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 and blinatumomab work in treating patients
      with B acute lymphoblastic leukemia that has come back or is not responding to treatment.
      Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell
      growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer
      cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating
      patients with relapsed or refractory B acute lymphoblastic leukemia.
PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or
      refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate.

      SECONDARY OBJECTIVES:

      I. To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with
      relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR
      with incomplete count recovery [CRi]), relapse free survival (RFS), overall survival (OS),
      minimal residual disease (MRD) response, proportion of patients bridged to allogeneic
      hematopoietic cell transplant (allo-HCT), and toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of CR
time frame: Up to 91 days
measure: Incidence of adverse events graded according to the National Cancer Institute CTCAE v4.03
time frame: Up to 6 months
measure: MRD response
time frame: Up to 6 months
measure: ORR defined as CR plus CRi assessed by disease-specific response criteria
time frame: Up to 6 months
measure: OS
time frame: From the time of first study drug administration until the date of progression or death from any cause, assessed for up to 6 months
measure: RFS
time frame: Time from CR/CRi until the date of progression or death from any cause, assessed for up to 6 months
arm group label: Treatment (ibrutinib, blinatumomab)
arm group type: Experimental
description: INDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Blinatumomab
description: Given IV
arm group label: Treatment (ibrutinib, blinatumomab)
other name: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
other name: Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
other name: Blincyto
other name: MEDI-538
other name: MT-103
intervention type: Drug
intervention name: Ibrutinib
description: Given PO
arm group label: Treatment (ibrutinib, blinatumomab)
other name: BTK Inhibitor PCI-32765
other name: CRA-032765
other name: Imbruvica
other name: PCI-32765
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brian Jonas
role: Principal Investigator
affiliation: University of California, Davis
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, Davis
investigator full name: Brian Jonas
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Philadelphia Chromosome
mesh term: Antineoplastic Agents, Immunological
mesh term: Blinatumomab
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Muromonab-CD3
mesh term: Antibodies, Bispecific