<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/NCT04402138</url>
  </required_header>
  <id_info>
    <org_study_id>LYM 155</org_study_id>
    <nct_id>NCT04402138</nct_id>
  </id_info>
  <brief_title>Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma</brief_title>
  <official_title>Single Arm, Phase II Study of Acalabrutinib as Post-Autologous Blood or Marrow Transplant (BMT) Maintenance Therapy in Subjects With Mantle Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SCRI Development Innovations, LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Acerta Pharma, LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>SCRI Development Innovations, LLC</source>
  <oversight_info>
    <has_dmc>No</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 phase II study to evaluate efficacy of Acalabrutinib as a maintenance therapy&#xD;
      following blood or marrow transplant (BMT) in patients who have been diagnosed with mantle&#xD;
      cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mantle cell lymphoma (MCL) is one of approximately 100 different types of non-Hodgkin's&#xD;
      lymphoma (NHL). Due to the aggressive and heterogeneous nature of MCL, majority of patients&#xD;
      are diagnosed with advanced stage disease that requires immediate, diverse and aggressive&#xD;
      courses of therapy to improve the outcome of the disease. The addition of blood or bone&#xD;
      marrow transplantation (BMT) to the chemotherapy regimens is a critical factor to prolong&#xD;
      duration of response in patients, however, the benefit of combination chemotherapy followed&#xD;
      by BMT is often temporary as patients experience disease progression and mortality and this&#xD;
      underscores the need for novel therapies as well as additional maintenance therapy strategies&#xD;
      to prevent relapse post-BMT.&#xD;
&#xD;
      Acalabrutinib, a selective, irreversible small molecule inhibitor of Bruton's tyrosine kinase&#xD;
      (BTK) is approved for the treatment of adult patients with MCL who have received at least 1&#xD;
      prior therapy&#xD;
&#xD;
      This study is a single arm, multi-center, phase 2 study of subjects who will receive&#xD;
      acalabrutinib as maintenance therapy post-BMT. Subjects will undergo a standard of care BMT&#xD;
      with conditioning regimen determined by the treating physician per institutional&#xD;
      guidelines.The BMT is not considered part of this study. Following completion of the BMT,&#xD;
      Maintenance therapy with acalabrutinib will begin on Day 100 in 28-day cycles. Subjects will&#xD;
      self-administer 100 mg acalabrutinib BID until they reach 2 years post-BMT (approximately 22&#xD;
      cycles).Subjects will be followed for up to 5 years post-BMT for Progression Free Survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 7, 2020</start_date>
  <completion_date type="Anticipated">August 7, 2027</completion_date>
  <primary_completion_date type="Anticipated">August 7, 2027</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>Progression Free Survival Rate (PFS)</measure>
    <time_frame>Assessed with CT/MRI/FGD-PET scans for up to 24 months</time_frame>
    <description>Progression Free Survival Rate is defined as the number of subjects who are alive and free of disease progression or relapse according to RECIL for up to 2 years post-BMT.&#xD;
According to RECIL, disease progression is defined as following criteria:&#xD;
&gt;20% increase in sum of longest diameters of target lesions.&#xD;
For small lymph nodes measuring &lt;15 mm post therapy, a minimum absolute increase of 5 mm and the longest diameter should exceed 15mm.&#xD;
Appearance of new lesions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Conversion rate from Minimal Residual Disease Positive (MRD+) to Minimal Residual Disease Negative (MRD-)</measure>
    <time_frame>Assessed at day +100 (prior to beginning maintenance), 6 months, 1 year and up to 2 years post-BMT</time_frame>
    <description>Proportion of patients whose whole blood and bone marrow results transition from MRD positive to MRD negative during therapy for up to 2 years post-BMT.&#xD;
An MRD Negative status will be defined as all results from whole blood and BM that are negative for the presence of residual clonal cells (with assay sensitivity of 10^-6) per Adaptive Biotechnologies' reporting methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD) correlation with Progression Free Survival (PFS)</measure>
    <time_frame>Assessed at day +100 post BMT (prior to beginning of maintenance), 6 months, 1 year and up to 2 years post-BMT</time_frame>
    <description>To compare the median PFS for MRD negative population with MRD positive population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse event</measure>
    <time_frame>Safety assessment will be done throughout the study for approximately 2 years</time_frame>
    <description>Number of Participants with grade 3,4 or 5 Adverse events/Serious Adverse events</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Acalabrutinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acalabrutinib will be self-administered orally for up to approximately 2 years post-BMT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acalabrutinib</intervention_name>
    <description>Acalabrutinib 100 mg BID will be self-administered orally starting from 100 day (+/- 7 days) Post-BMT on a 28-day schedule, with or without food, until the patient has reached approximately 2 years post-BMT.</description>
    <arm_group_label>Acalabrutinib</arm_group_label>
    <other_name>Calquence</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria for Initial Enrollment (Screening #1):&#xD;
&#xD;
        Patients must meet all of the following criteria in order to be included in this research&#xD;
        study:&#xD;
&#xD;
          1. Written informed consent, according to local guidelines, signed by the subject or by a&#xD;
             legal guardian prior to the performance of any study-related screening procedures.&#xD;
&#xD;
          2. Men and women ≥18 years-of-age at the time of signature of the informed consent form&#xD;
             (ICF).&#xD;
&#xD;
          3. A diagnosis of MCL confirmed by one of the following:&#xD;
&#xD;
               -  t(11;14) detected by fluorescence in situ hybridization (FISH), conventional&#xD;
                  cytogenetics, or other molecular evaluation&#xD;
&#xD;
               -  expression of cyclin D1 confirmed by immunohistochemistry.&#xD;
&#xD;
          4. Subject must have completed induction chemotherapy and plan to and be eligible to&#xD;
             receive their first BMT per standard of care.&#xD;
&#xD;
          5. Availability of an archival paraffin-embedded tumor block for MRD testing.&#xD;
&#xD;
          6. The Investigator anticipates that the subject will meet the appropriate lab&#xD;
             requirements listed in Screening #2 by Day 100.&#xD;
&#xD;
          7. Patients who received prior therapy with a BTK inhibitor are eligible to enroll.&#xD;
&#xD;
        Inclusion Criteria Post-BMT, Prior to Day 100 (Screening #2):&#xD;
&#xD;
          1. Adequate organ system function defined as:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1,000/mm3.&#xD;
&#xD;
               -  Total bilirubin ≤1.5 x the upper limit of normal (ULN) (except for previously&#xD;
                  documented Gilbert's syndrome)&#xD;
&#xD;
               -  Platelet count ≥75,000/mm3. Platelet infusions to meet eligibility criteria are&#xD;
                  not allowed within 3 days of study enrollment.&#xD;
&#xD;
               -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN&#xD;
&#xD;
               -  Calculated creatinine clearance (CrCl) ≥30 mL/min as calculated by the&#xD;
                  CockcroftGault method. Estimated CrCl (glomerular filtration rate [GFR]) =&#xD;
                  (140-age [years]) x (weight [kg]) x Fa /(72 x serum creatinine [mg/dL]) a where F&#xD;
                  = 0.85 for females and F = 1 for males&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.&#xD;
&#xD;
          3. Subjects who did not receive an anti-cancer therapy (including surgery, radiotherapy,&#xD;
             chemotherapy, immunotherapy, or investigational therapy) during the time between their&#xD;
             transplant and the start of study therapy. Subjects must have recovered (e.g., Grade&#xD;
             ≤1 or baseline) from AEs associated with prior cancer therapy. Note: Subjects with&#xD;
             Grade ≤2 neuropathy or Grade ≤2 alopecia are an exception to the latter criterion and&#xD;
             may qualify for the study.&#xD;
&#xD;
          4. Woman of childbearing potential (WoCBP) who are sexually active with male partners&#xD;
             must use highly effective methods of contraception during treatment and for 2 days&#xD;
             after the last dose of acalabrutinib. For male subjects with a pregnant or&#xD;
             non-pregnant WoCBP partner, no contraception measures are required. A WoCBP must have&#xD;
             a negative pregnancy test (urine or serum) at the time of screening and 72 hours&#xD;
             before starting the study drug or have evidence of non-childbearing potential by&#xD;
             fulfilling one of the following criteria:&#xD;
&#xD;
               -  Post-menopausal women, defined as either women aged &gt;50 years and amenorrheic for&#xD;
                  ≥12 months following cessation of all exogenous hormonal treatments or women &lt;50&#xD;
                  years old who have been amenorrheic for ≥12 months following the cessation of&#xD;
                  exogenous hormonal treatments, and have serum follicle- stimulating hormone (FSH)&#xD;
                  and luteinizing hormone (LH) levels in the post- menopausal range for the&#xD;
                  institution.&#xD;
&#xD;
               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral&#xD;
                  oophorectomy or bilateral salpingectomy, but not tubal ligation&#xD;
&#xD;
               -  Medically confirmed, irreversible premature ovarian failure.&#xD;
&#xD;
          5. Willing and able to participate in all required evaluations and procedures in this&#xD;
             study protocol including swallowing capsules without difficulty.&#xD;
&#xD;
          6. Ability to understand the purpose and risks of the study and provide signed and dated&#xD;
             informed consent and authorization to use protected health information (PHI).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who meet any of the following criteria will be excluded from study entry:&#xD;
&#xD;
          1. Subjects who have relapsed or progressed at any time prior to BM&#xD;
&#xD;
          2. Subjects with known mutations that confer resistance to a BTK inhibitor.&#xD;
&#xD;
          3. Confirmed clinical PD since the time of BMT&#xD;
&#xD;
          4. Prior malignancy (or any other malignancy requiring active treatment), except for&#xD;
             adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,&#xD;
             or other cancer from which the subject has been disease free for ≥2 years or that will&#xD;
             not limit survival to &lt;2 years. The exceptions are:&#xD;
&#xD;
               -  Subjects treated with curative intent &gt;2 years prior to enrollment and have a low&#xD;
                  probability of recurrence.&#xD;
&#xD;
          5. Clinically significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of&#xD;
             screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart&#xD;
             Association Functional Classification.&#xD;
&#xD;
          6. Malabsorption syndrome, disease significantly affecting gastrointestinal function,&#xD;
             resection of the stomach or small bowel that is likely to affect absorption,&#xD;
             symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or&#xD;
             gastric restrictions and bariatric surgery, such as gastric bypass.&#xD;
&#xD;
          7. Known history of infection with human immunodeficiency virus (HIV) or any uncontrolled&#xD;
             active systemic bacterial, fungal, parasitic or viral infection. Infections are&#xD;
             considered controlled if appropriate therapy has been instituted and, at the time of&#xD;
             screening, no signs of infection progression are present.&#xD;
&#xD;
          8. Known history of drug-specific hypersensitivity or anaphylaxis to study drug&#xD;
             (including active product or excipient components).&#xD;
&#xD;
          9. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand&#xD;
             disease).&#xD;
&#xD;
         10. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.&#xD;
&#xD;
         11. Requires treatment with a strong CYP3A4 inhibitor/inducer&#xD;
&#xD;
         12. Requires or is receiving anticoagulation treatment with warfarin or equivalent vitamin&#xD;
             K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.&#xD;
&#xD;
         13. Prothrombin time (PT)/ international normalized ratio (INR) or activated partial&#xD;
             thromboplastin time (aPTT) &gt;2 x ULN (in the absence of lupus anticoagulant).&#xD;
&#xD;
         14. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole,&#xD;
             lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving&#xD;
             proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible&#xD;
             for enrollment to this study.&#xD;
&#xD;
         15. History of significant cerebrovascular disease/event, including stroke or intracranial&#xD;
             hemorrhage, within 6 months before the first dose of study drug.&#xD;
&#xD;
         16. Major surgical procedure within 28 days of first dose of study drug. Note: If a&#xD;
             subject had major surgery, they must have recovered adequately from any toxicity&#xD;
             and/or complications from the intervention before the first dose of study drug.&#xD;
&#xD;
         17. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody&#xD;
             (anti-HBc) positive and who are hepatitis B surface antigen (HbsAg) negative will need&#xD;
             to have a negative PCR result. Those who are HbsAg positive or hepatitis B PCR&#xD;
             positive will be excluded. Subjects who are hepatitis C antibody positive will need to&#xD;
             have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.&#xD;
&#xD;
         18. Breastfeeding or pregnant.&#xD;
&#xD;
         19. Concurrent participation in another therapeutic clinical trial.&#xD;
&#xD;
         20. Psychological, familial, sociological, or geographical conditions that do not permit&#xD;
             compliance with the protocol and/or follow-up procedures outlined in the protocol.&#xD;
&#xD;
         21. The inability to swallow capsules.&#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>Ian Flinn, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>SCRI Development Innovations, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane University, Office of Clinical Research</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCA Midwest</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>January 13, 2023</last_update_submitted>
  <last_update_submitted_qc>January 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acalabrutinib</keyword>
  <keyword>Non Hodgkin's lymphoma</keyword>
  <keyword>Blood or Marrow transplant</keyword>
  <keyword>BMT</keyword>
  <keyword>Maintenance therapy</keyword>
  <keyword>Bruton's Tyrosine Kinase Inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acalabrutinib</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/NCT04402138
org study id: LYM 155
nct id: NCT04402138
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II study to evaluate efficacy of Acalabrutinib as a maintenance therapy
      following blood or marrow transplant (BMT) in patients who have been diagnosed with mantle
      cell lymphoma.
Mantle cell lymphoma (MCL) is one of approximately 100 different types of non-Hodgkin's
      lymphoma (NHL). Due to the aggressive and heterogeneous nature of MCL, majority of patients
      are diagnosed with advanced stage disease that requires immediate, diverse and aggressive
      courses of therapy to improve the outcome of the disease. The addition of blood or bone
      marrow transplantation (BMT) to the chemotherapy regimens is a critical factor to prolong
      duration of response in patients, however, the benefit of combination chemotherapy followed
      by BMT is often temporary as patients experience disease progression and mortality and this
      underscores the need for novel therapies as well as additional maintenance therapy strategies
      to prevent relapse post-BMT.

      Acalabrutinib, a selective, irreversible small molecule inhibitor of Bruton's tyrosine kinase
      (BTK) is approved for the treatment of adult patients with MCL who have received at least 1
      prior therapy

      This study is a single arm, multi-center, phase 2 study of subjects who will receive
      acalabrutinib as maintenance therapy post-BMT. Subjects will undergo a standard of care BMT
      with conditioning regimen determined by the treating physician per institutional
      guidelines.The BMT is not considered part of this study. Following completion of the BMT,
      Maintenance therapy with acalabrutinib will begin on Day 100 in 28-day cycles. Subjects will
      self-administer 100 mg acalabrutinib BID until they reach 2 years post-BMT (approximately 22
      cycles).Subjects will be followed for up to 5 years post-BMT for Progression Free Survival.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival Rate (PFS)
time frame: Assessed with CT/MRI/FGD-PET scans for up to 24 months
description: Progression Free Survival Rate is defined as the number of subjects who are alive and free of disease progression or relapse according to RECIL for up to 2 years post-BMT.
According to RECIL, disease progression is defined as following criteria:
>20% increase in sum of longest diameters of target lesions.
For small lymph nodes measuring <15 mm post therapy, a minimum absolute increase of 5 mm and the longest diameter should exceed 15mm.
Appearance of new lesions
measure: Conversion rate from Minimal Residual Disease Positive (MRD+) to Minimal Residual Disease Negative (MRD-)
time frame: Assessed at day +100 (prior to beginning maintenance), 6 months, 1 year and up to 2 years post-BMT
description: Proportion of patients whose whole blood and bone marrow results transition from MRD positive to MRD negative during therapy for up to 2 years post-BMT.
An MRD Negative status will be defined as all results from whole blood and BM that are negative for the presence of residual clonal cells (with assay sensitivity of 10^-6) per Adaptive Biotechnologies' reporting methods.
measure: Minimal Residual Disease (MRD) correlation with Progression Free Survival (PFS)
time frame: Assessed at day +100 post BMT (prior to beginning of maintenance), 6 months, 1 year and up to 2 years post-BMT
description: To compare the median PFS for MRD negative population with MRD positive population
measure: Incidence of Adverse event
time frame: Safety assessment will be done throughout the study for approximately 2 years
description: Number of Participants with grade 3,4 or 5 Adverse events/Serious Adverse events
arm group label: Acalabrutinib
arm group type: Experimental
description: Acalabrutinib will be self-administered orally for up to approximately 2 years post-BMT.
intervention type: Drug
intervention name: Acalabrutinib
description: Acalabrutinib 100 mg BID will be self-administered orally starting from 100 day (+/- 7 days) Post-BMT on a 28-day schedule, with or without food, until the patient has reached approximately 2 years post-BMT.
arm group label: Acalabrutinib
other name: Calquence
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ian Flinn, MD, PhD
role: Study Director
affiliation: SCRI Development Innovations, LLC
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Mantle-Cell
mesh term: Acalabrutinib