<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/NCT03232307</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0280</org_study_id>
    <secondary_id>NCI-2018-01271</secondary_id>
    <secondary_id>2016-0280</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <nct_id>NCT03232307</nct_id>
  </id_info>
  <brief_title>Ibrutinib Plus Rituximab and Lenalidomide in Treating Elderly Participants With Newly Diagnosed Mantle Cell Lymphoma</brief_title>
  <official_title>A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed MCL</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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 plus rituximab and lenalidomide work in&#xD;
      treating elderly participants with newly diagnosed mantle cell lymphoma. Ibrutinib may stop&#xD;
      the growth of cancer cells by blocking some of the enzymes needed for cell growth.&#xD;
      Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune&#xD;
      system attack the cancer, and may interfere with the ability of tumor cells to grow and&#xD;
      spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the&#xD;
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by&#xD;
      stopping them from spreading. Giving ibrutinib plus rituximab and lenalidomide may work&#xD;
      better in treating elderly participants with newly diagnosed mantle cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the overall response rate (ORR) at 4 months of ibrutinib plus rituximab and&#xD;
      lenalidomide in elderly patients with newly-diagnosed, untreated mantle cell lymphoma (MCL).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the toxicity profile of the combination of ibrutinib plus rituximab and&#xD;
      lenalidomide in newly diagnosed, untreated MCL.&#xD;
&#xD;
      II. To estimate the overall response rate (ORR); (partial response [PR] or better), the&#xD;
      response duration (DOR), progression-free survival (PFS), time to progression (TTP) and&#xD;
      overall survival (OS). Clinical benefit response [(CBR) = marginal response (MR) + ORR] will&#xD;
      also be evaluated.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Correlative studies will be aimed at confirming the mechanism of action of the combination&#xD;
      and to identify predictors of response or resistance to therapy.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Participants receive ibrutinib orally (PO) on days 1-28. Courses repeat every 28 days in the&#xD;
      absence of disease progression or unacceptable toxicity. Participants also receive rituximab&#xD;
      intravenously (IV) on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and&#xD;
      then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone&#xD;
      PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for&#xD;
      1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, participants are followed up at 30 days, every 3 months&#xD;
      for 1 year, and every 6 months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Sponsor does not wish to proceed&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 1, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 1, 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>Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma</measure>
    <time_frame>At 4 months (each cycle is 28 days)</time_frame>
    <description>The overall response (complete response + partial response) at four months and toxicity at one month (during course 1) will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Independence was assumed between or and toxicity, where toxicity is defined as dose-limiting toxicity (DLT) within cycle 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03</measure>
    <time_frame>At 1 month (cycle 1 is 28 days)</time_frame>
    <description>Toxicity data by type and severity will be summarized by frequency tables. For the efficacy endpoints, intend-to-treat analysis will be performed. For the toxicity endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>CCND1 Positive</condition>
  <condition>CD20-Positive Neoplastic Cells Present</condition>
  <condition>Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)</arm_group_label>
    <other_name>Aacidexam</other_name>
    <other_name>Adexone</other_name>
    <other_name>Aknichthol Dexa</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Alin</other_name>
    <other_name>Alin Depot</other_name>
    <other_name>Alin Oftalmico</other_name>
    <other_name>Amplidermis</other_name>
    <other_name>Anemul mono</other_name>
    <other_name>Auricularum</other_name>
    <other_name>Auxiloson</other_name>
    <other_name>Baycuten</other_name>
    <other_name>Baycuten N</other_name>
    <other_name>Cortidexason</other_name>
    <other_name>Cortisumman</other_name>
    <other_name>Decacort</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decalix</other_name>
    <other_name>Decameth</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Dectancyl</other_name>
    <other_name>Dekacort</other_name>
    <other_name>Deltafluorene</other_name>
    <other_name>Deronil</other_name>
    <other_name>Desamethasone</other_name>
    <other_name>Desameton</other_name>
    <other_name>Dexa-Mamallet</other_name>
    <other_name>Dexa-Rhinosan</other_name>
    <other_name>Dexa-Scheroson</other_name>
    <other_name>Dexa-sine</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Dexacortin</other_name>
    <other_name>Dexafarma</other_name>
    <other_name>Dexafluorene</other_name>
    <other_name>Dexalocal</other_name>
    <other_name>Dexamecortin</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dexamethasonum</other_name>
    <other_name>Dexamonozon</other_name>
    <other_name>Dexapos</other_name>
    <other_name>Dexinoral</other_name>
    <other_name>Dexone</other_name>
    <other_name>Dinormon</other_name>
    <other_name>Fluorodelta</other_name>
    <other_name>Fortecortin</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadecadrol</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Lokalison-F</other_name>
    <other_name>Loverine</other_name>
    <other_name>Methylfluorprednisolone</other_name>
    <other_name>Millicorten</other_name>
    <other_name>Mymethasone</other_name>
    <other_name>Orgadrone</other_name>
    <other_name>Spersadex</other_name>
    <other_name>Visumetazone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)</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>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)</arm_group_label>
    <other_name>ABP 798</other_name>
    <other_name>BI 695500</other_name>
    <other_name>C2B8 Monoclonal Antibody</other_name>
    <other_name>Chimeric Anti-CD20 Antibody</other_name>
    <other_name>CT-P10</other_name>
    <other_name>IDEC-102</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 Monoclonal Antibody</other_name>
    <other_name>MabThera</other_name>
    <other_name>Monoclonal Antibody IDEC-C2B8</other_name>
    <other_name>PF-05280586</other_name>
    <other_name>Rituxan</other_name>
    <other_name>Rituximab Biosimilar ABP 798</other_name>
    <other_name>Rituximab Biosimilar BI 695500</other_name>
    <other_name>Rituximab Biosimilar CT-P10</other_name>
    <other_name>Rituximab Biosimilar GB241</other_name>
    <other_name>Rituximab Biosimilar IBI301</other_name>
    <other_name>Rituximab Biosimilar PF-05280586</other_name>
    <other_name>Rituximab Biosimilar RTXM83</other_name>
    <other_name>Rituximab Biosimilar SAIT101</other_name>
    <other_name>RTXM83</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.&#xD;
&#xD;
          -  Ki-67 &gt;= 50%.&#xD;
&#xD;
          -  Patients must have never received any prior systemic therapy for their disease.&#xD;
&#xD;
          -  Sign (or their legally-acceptable representatives must sign) an informed consent&#xD;
             document indicating that they understand the purpose of and procedures required for&#xD;
             the study and are willing to participate in the study.&#xD;
&#xD;
          -  Patients should in general have bi-dimensional measurable disease using the Cheson&#xD;
             criteria (measurable disease by computed tomography [CT] scan defined as at least 1&#xD;
             lesion that measures &gt;= 1.5 cm in single dimension) (bone marrow or gastrointestinal&#xD;
             [GI] only involvement is acceptable).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3 without transfusion support.&#xD;
&#xD;
          -  Platelet count &gt; 100,000/mm^3. Patients who have bone marrow infiltration by MCL are&#xD;
             eligible if their platelet level is &gt;= 50,000 /mm^3 independent of platelet&#xD;
             transfusions.&#xD;
&#xD;
          -  Aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and&#xD;
             aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =&lt; 3 x upper limit&#xD;
             of normal.&#xD;
&#xD;
          -  Serum bilirubin &lt; 1.5 mg/dl unless bilirubin rise is due to Gilbert's syndrome or of&#xD;
             non-hepatic origin.&#xD;
&#xD;
          -  Creatinine (Cr) clearance &gt;= 25 mL/min (per Cockcroft-Gault equation).&#xD;
&#xD;
          -  Disease free of prior malignancies of equal to or greater than 6 months with exception&#xD;
             of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma &quot;in&#xD;
             situ&quot; of the cervix or breast, or other malignancies in remission (including prostate&#xD;
             cancer patients in remission from radiation therapy, surgery or brachytherapy), not&#xD;
             actively being treated, with a life expectancy &gt; 3 years.&#xD;
&#xD;
          -  Patients must be willing to receive transfusions of blood products.&#xD;
&#xD;
          -  Willing and able to participate in all study related procedures and therapy including&#xD;
             swallowing capsules without difficulty.&#xD;
&#xD;
          -  Men must agree 1) to use a latex condom during sexual contact with a female of&#xD;
             childbearing potential (FCBP) even if they have had a vasectomy from the time of&#xD;
             signing the informed consent form through 90 days after the last dose of lenalidomide&#xD;
             and ibrutinib; 2) to not donate sperm during and after the study. Females of&#xD;
             childbearing potential (FCBP) must have a negative serum or urine pregnancy test with&#xD;
             a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24&#xD;
             hours of starting lenalidomide and must either commit to continued abstinence from&#xD;
             heterosexual intercourse or begin TWO acceptable methods of birth control, one highly&#xD;
             effective method and one additional effective method AT THE SAME TIME, at least 28&#xD;
             days before she starts taking lenalidomide through 90 days and ibrutinib through 30&#xD;
             days after the last dose of study drug. FCBP must also agree to ongoing pregnancy&#xD;
             testing.&#xD;
&#xD;
          -  All patients must be registered in and must comply with all requirements of the&#xD;
             Revlimid Rems program.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious medical condition that, in the investigator opinion, places the patient at&#xD;
             unacceptable risk and/or would prevent the subject from signing the informed consent&#xD;
             form. Examples include but are not limited to, uncontrolled hypertension, uncontrolled&#xD;
             diabetes mellitus, active/symptomatic coronary artery disease, active infection&#xD;
             requiring treatment with intravenous (IV) antibiotics, antiviral or antifungal agents,&#xD;
             active hemorrhage, or psychiatric illness in the investigator's opinion places the&#xD;
             patient at unacceptable risk and would prevent the subject from signing the informed&#xD;
             consent form.&#xD;
&#xD;
          -  Pregnant or breastfeeding females.&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) infection. Patients with active hepatitis B&#xD;
             infection (not including patients with prior hepatitis B vaccination; or positive&#xD;
             serum hepatitis B antibody). Known hepatitis C infection is allowed as long as there&#xD;
             is no active disease. These patients should be optimized by GI consultation for&#xD;
             hepatitis B and infectious disease consult for hepatitis C.&#xD;
&#xD;
          -  The patient has a prior or concurrent malignancy that in the opinion of the&#xD;
             investigator, presents a greater risk to the patient's health and survival, than of&#xD;
             the MCL, within the subsequent 6 months at the time of consent.&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 6 months prior to signing the&#xD;
             consent.&#xD;
&#xD;
          -  Patients at high-risk for thromboembolic disease, such as those with prior heterotopic&#xD;
             ossification (h/o) deep venous thrombosis (DVT).&#xD;
&#xD;
          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, congestive heart failure or myocardial infarction within 6 months at the&#xD;
             time of consent or any class 3 (moderate) or 4 (severe) cardiac disease defined by the&#xD;
             New York Heart Association classification.&#xD;
&#xD;
          -  Significant screening electrocardiogram (ECG) abnormalities including left bundle&#xD;
             branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block,&#xD;
             bradycardia (&lt; 50 beats per minute [bpm]), or corrected QT (QTc) &gt; 500 msec.&#xD;
&#xD;
          -  Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.&#xD;
&#xD;
          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or&#xD;
             resection of the stomach or small bowel or ulcerative colitis, symptomatic&#xD;
             inflammatory bowel disease, or partial or complete bowel obstruction.&#xD;
&#xD;
          -  Major surgery or wound that has not fully healed within 4 weeks or vaccination with&#xD;
             live attenuated vaccines within 4 weeks of the first dose of study drugs.&#xD;
&#xD;
          -  Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist.&#xD;
&#xD;
          -  Requires treatment with strong cytochrome P4503A (CYP3A) inhibitors.&#xD;
&#xD;
          -  All patients with central nervous system lymphoma.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>66 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luhua (Michael) Wang</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>August 20, 2019</last_update_submitted>
  <last_update_submitted_qc>August 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>BB 1101</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/NCT03232307
org study id: 2016-0280
secondary id: NCI-2018-01271
secondary id: 2016-0280
secondary id: P30CA016672
nct id: NCT03232307
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well ibrutinib plus rituximab and lenalidomide work in
      treating elderly participants with newly diagnosed mantle cell lymphoma. Ibrutinib may stop
      the growth of cancer cells by blocking some of the enzymes needed for cell growth.
      Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune
      system attack the cancer, and may interfere with the ability of tumor cells to grow and
      spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Giving ibrutinib plus rituximab and lenalidomide may work
      better in treating elderly participants with newly diagnosed mantle cell lymphoma.
PRIMARY OBJECTIVES:

      I. To evaluate the overall response rate (ORR) at 4 months of ibrutinib plus rituximab and
      lenalidomide in elderly patients with newly-diagnosed, untreated mantle cell lymphoma (MCL).

      SECONDARY OBJECTIVES:

      I. To evaluate the toxicity profile of the combination of ibrutinib plus rituximab and
      lenalidomide in newly diagnosed, untreated MCL.

      II. To estimate the overall response rate (ORR); (partial response [PR] or better), the
      response duration (DOR), progression-free survival (PFS), time to progression (TTP) and
      overall survival (OS). Clinical benefit response [(CBR) = marginal response (MR) + ORR] will
      also be evaluated.

      EXPLORATORY OBJECTIVES:

      I. Correlative studies will be aimed at confirming the mechanism of action of the combination
      and to identify predictors of response or resistance to therapy.

      OUTLINE:

      Participants receive ibrutinib orally (PO) on days 1-28. Courses repeat every 28 days in the
      absence of disease progression or unacceptable toxicity. Participants also receive rituximab
      intravenously (IV) on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and
      then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone
      PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for
      1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 days, every 3 months
      for 1 year, and every 6 months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma
time frame: At 4 months (each cycle is 28 days)
description: The overall response (complete response + partial response) at four months and toxicity at one month (during course 1) will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Independence was assumed between or and toxicity, where toxicity is defined as dose-limiting toxicity (DLT) within cycle 1.
measure: Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03
time frame: At 1 month (cycle 1 is 28 days)
description: Toxicity data by type and severity will be summarized by frequency tables. For the efficacy endpoints, intend-to-treat analysis will be performed. For the toxicity endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.
measure: Overall survival (OS)
time frame: Up to 4 years
description: Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.
measure: Progression-free survival
time frame: Up to 4 years
description: Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.
arm group label: Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
arm group type: Experimental
description: Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Dexamethasone
description: Given PO
arm group label: Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
other name: Aacidexam
other name: Adexone
other name: Aknichthol Dexa
other name: Alba-Dex
other name: Alin
other name: Alin Depot
other name: Alin Oftalmico
other name: Amplidermis
other name: Anemul mono
other name: Auricularum
other name: Auxiloson
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decalix
other name: Decameth
other name: Decasone R.p.
other name: Dectancyl
other name: Dekacort
other name: Deltafluorene
other name: Deronil
other name: Desamethasone
other name: Desameton
other name: Dexa-Mamallet
other name: Dexa-Rhinosan
other name: Dexa-Scheroson
other name: Dexa-sine
other name: Dexacortal
other name: Dexacortin
other name: Dexafarma
other name: Dexafluorene
other name: Dexalocal
other name: Dexamecortin
other name: Dexameth
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Fluorodelta
other name: Fortecortin
other name: Gammacorten
other name: Hexadecadrol
other name: Hexadrol
other name: Lokalison-F
other name: Loverine
other name: Methylfluorprednisolone
other name: Millicorten
other name: Mymethasone
other name: Orgadrone
other name: Spersadex
other name: Visumetazone
intervention type: Drug
intervention name: Ibrutinib
description: Given PO
arm group label: Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
other name: BTK Inhibitor PCI-32765
other name: CRA-032765
other name: Imbruvica
other name: PCI-32765
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
other name: ABP 798
other name: BI 695500
other name: C2B8 Monoclonal Antibody
other name: Chimeric Anti-CD20 Antibody
other name: CT-P10
other name: IDEC-102
other name: IDEC-C2B8
other name: IDEC-C2B8 Monoclonal Antibody
other name: MabThera
other name: Monoclonal Antibody IDEC-C2B8
other name: PF-05280586
other name: Rituxan
other name: Rituximab Biosimilar ABP 798
other name: Rituximab Biosimilar BI 695500
other name: Rituximab Biosimilar CT-P10
other name: Rituximab Biosimilar GB241
other name: Rituximab Biosimilar IBI301
other name: Rituximab Biosimilar PF-05280586
other name: Rituximab Biosimilar RTXM83
other name: Rituximab Biosimilar SAIT101
other name: RTXM83
criteria: 
gender: All
minimum age: 66 Years
maximum age: N/A
healthy volunteers: No
last name: Luhua (Michael) Wang
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Mantle-Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Rituximab
mesh term: Antineoplastic Agents, Immunological
mesh term: Lenalidomide
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: BB 1101