Clinical Trials /

Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed Mantle Cell Lymphoma (MCL)

NCT03232307

Description:

The goal of this clinical research study is to learn if a combination of ibrutinib, rituximab, and lenalidomide can help control newly diagnosed mantle cell lymphoma (MCL) in patients over 65. The safety of this drug combination will also be studied.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed Mantle Cell Lymphoma (MCL)
  • Official Title: A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed Mantle Cell Lymphoma (MCL)

Clinical Trial IDs

  • ORG STUDY ID: 2016-0280
  • NCT ID: NCT03232307

Conditions

  • Hematopoietic/Lymphoid Cancer
  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
IbrutinibPCI-32765, ImbruvicaIbrutinib + Rituximab + Lenalidomide
RituximabRituxanIbrutinib + Rituximab + Lenalidomide
LenalidomideCC-5013, RevlimidIbrutinib + Rituximab + Lenalidomide
Dexamethasone Sodium SulfateDecadronIbrutinib + Rituximab + Lenalidomide

Purpose

The goal of this clinical research study is to learn if a combination of ibrutinib, rituximab, and lenalidomide can help control newly diagnosed mantle cell lymphoma (MCL) in patients over 65. The safety of this drug combination will also be studied.

Detailed Description

      Study Drug Administration:

      Each cycle is 28 days.

      If participant is found to be eligible to take part in this study, participant will take 4
      ibrutinib capsules with 1 cup (about 8 ounces) of water each day. Participant should take
      ibrutinib in the morning and at the same time as participant takes lenalidomide (described
      below). Do not open the capsules or dissolve them.

      If participant misses a dose, participant can take it up to 6 hours after the time
      participant would have taken it. If it is later than 6 hours, participant should skip the
      dose and start taking the capsules at the same time as usual the next day. Participant will
      need to fill out diary cards with information about when participant takes ibrutinib.
      Participant should bring the diary cards with participant to appointments. Participant will
      receive a 30 day supply of the ibrutinib capsules on Day 1 of Cycles 1-11. After that,
      starting on Cycle 12 and then every other cycle after that (Cycles 14, 16, and so on),
      participant will receive a 60-day supply of the drug every other cycle.

      Participant will take lenalidomide by mouth on Days 1-21 of each cycle. Participant should
      take lenalidomide at the same time each day. Participant should take it with a glass of water
      on either a full or an empty stomach. Participant should not break, chew, or open the
      capsules.

      If participant misses a dose of lenalidomide, participant should take it as soon as
      participant remembers on the same day. If participant misses taking participant's dose for
      the entire day, participant should take participant's regular dose the next scheduled day.
      Participant should not take double participant's regular dose to make up for a missed dose.

      If participant takes more than the prescribed dose of lenalidomide, participant should seek
      emergency medical care if needed and contact study staff right away.

      Participant will also be given standard drugs to help decrease the risk of side effects.
      Participant may ask the study staff for information about how the drugs are given and their
      risks.

      Participant will receive rituximab by vein on Days 1, 8, 15, and 22 of Cycles 1 and 2. After
      that, participant will receive rituximab by vein on Day 1 of Cycles 3-8 and then every other
      cycle after that (Cycles 10, 12, 14, and so on). The first dose should take about 6-8 hours.
      After that, each dose should take about 4 hours.

      If the doctor thinks it is in participant's best interest, participant may receive rituximab
      for a period of over 2 days. Participant's doctor will tell if participant will receive the
      dose over 2 days.

      Length of Study:

      Participant may continue taking ibrutinib for as long as the doctor thinks it is in
      participant's best interest. Participant may continue taking lenalidomide for up to 1 year.
      Participant may continue taking rituximab for up to 2 years. Participant will no longer be
      able to take the drug if the disease gets worse, if intolerable side effects occur, or if
      participant is unable to follow study directions.

      Participation will be over after follow-up.

      Study Visits:

      On Day 1 of Cycle 1:

        -  Blood (about 2 tablespoons) will be drawn to check the status of the disease and for
           biomarker testing, which may include genetic biomarkers. Biomarkers are found in the
           blood and may be related to participant's reaction to the study drug.

        -  Blood (about 2 tablespoons) will be drawn to check participant's immune system.

        -  Blood (about 2 tablespoons) will be drawn for tumor lysis syndrome monitoring if needed.

      On Day 1 of Cycles 1-12 and then every other cycle after that (Cycles 14, 16, 18, and so on):

        -  Participant will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests.

      On Days 8, 15, and 22 of Cycle 1, blood (about 3 tablespoons) will be drawn for routine tests
      and tumor lysis syndrome monitoring if needed.

      On Day 1 of Cycles 2, 4, 6, 8, then every 4 cycles after that (Cycles 12, 16, 20, and so on),
      participant will have a CT scan to check the status of the disease. If the doctor thinks it
      is in participant's best interest, participant may have these scans less often.

      One (1) time between Cycles 2-10, when the study doctor thinks it is needed or if the disease
      gets worse, blood (about 4 tablespoons) will be drawn for biomarker testing and to check
      participant's immune system.

      Every 14 days, if the doctor thinks it is needed and if participant is able to become
      pregnant, blood (about 1½ tablespoons) or urine will be collected for a pregnancy test.

      At any time during the study, if the study doctor thinks it is needed:

        -  Participant may have a bone marrow biopsy and/or aspiration.

        -  Participant may have a gastrointestinal endoscopy.

        -  Participant may have a PET/CT scan

        -  If participant can become pregnant, blood (about 1½ tablespoons) or urine may be
           collected for a pregnancy test.

      End-of-Treatment Visit:

      Within 30 days after participant's last dose of study drugs:

        -  Participant will have a physical exam.

        -  Participant will have an EKG.

        -  Blood (about 5-7 tablespoons) will be drawn for routine tests, for biomarker testing,
           for immune system testing, and to check the status of the disease.

        -  Participant will have an x-ray.

        -  If the doctor thinks it is needed, participant will have a CT scan and/or a PET/CT scan
           to check the status of the disease.

        -  If the doctor thinks it is needed, participant will have a gastrointestinal endoscopy to
           check the status of the disease.

        -  If the doctor thinks it is needed, participant will have a bone marrow biopsy and/or
           aspirate to check the status of the disease.

        -  If participant can become pregnant, blood (about 1½ tablespoons) or urine will be
           collected for a pregnancy test.

      Long Term Follow-Up:

      After participant's end-of-treatment visit, a member of the study staff will contact
      participant by phone every 3 months for 1 year and then every 6 months after that to see how
      participant is doing. These calls will take about 2-3 minutes.

      This is an investigational study. Ibrutinib is FDA approved and commercially available for
      the treatment of MCL. Rituximab is FDA approved for the treatment of non-Hodgkin's lymphoma
      and certain types of leukemia. Lenalidomide is FDA approved for the treatment of
      non-Hodgkin's lymphoma.

      The use of these drugs in combination is investigational. The study doctor can explain how
      the study drugs are designed to work.

      Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib + Rituximab + LenalidomideExperimentalIbrutinib by mouth each day. Lenalidomide by mouth on Days 1-21. Rituximab by vein on Days 1, 8, 15, and 22 of Cycles 1 and 2. After that, Rituximab by vein on Day 1 of Cycles 3-8 and then every other cycle after that (Cycles 10, 12, 14, and so on). Study cycles are 28 days.
  • Ibrutinib
  • Rituximab
  • Lenalidomide
  • Dexamethasone Sodium Sulfate

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.

          2. Ki-67 >/= 50%.

          3. Patients must have never received any prior systemic therapy for their disease.

          4. Sign (or their legally-acceptable representatives must sign) an informed consent
             document indicating that they understand the purpose of and procedures required for
             the study and are willing to participate in the study.

          5. Age > 65 years at the time of signing the informed consent.

          6. Patients should in general have bi-dimensional measurable disease using the Cheson
             criteria (Measureable disease by computed tomography (CT) scan defined as at least 1
             lesion that measures =/>1.5 cm in single dimension) (bone marrow or gastrointestinal
             (GI) only involvement is acceptable).

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

          8. Absolute neutrophil count (ANC) >/= 1000/mm^3 without transfusion support

          9. Platelet count > 100,000/mm^3. Patients who have bone marrow infiltration by MCL are
             eligible if their platelet level is >/= 50,000 /mm^3 independent of platelet
             transfusions.

         10. aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
             aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) </= 3 x upper limit
             of normal.

         11. Serum bilirubin <1.5 mg/dl unless bilirubin rise is due to Gilbert's syndrome or of
             non-hepatic origin

         12. Creatinine (Cr) Clearance >/= 25 mL/min (per Cockcroft-Gault Equation ),

         13. Disease free of prior malignancies of equal to or greater than 6 months with exception
             of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in
             situ" of the cervix or breast, or other malignancies in remission (including prostate
             cancer patients in remission from radiation therapy, surgery or brachytherapy), not
             actively being treated, with a life expectancy > 3 years.

         14. Patients must be willing to receive transfusions of blood products.

         15. Willing and able to participate in all study related procedures and therapy including
             swallowing capsules without difficulty.

         16. Men must agree 1) to use a latex condom during sexual contact with a FCBP even if they
             have had a vasectomy from the time of signing the informed consent form through 90
             days after the last dose of lenalidomide and ibrutinib;2) to not donate sperm during
             and after the study. Females of childbearing potential (FCBP)* must have a negative
             serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14
             days prior to and again within 24 hours of starting lenalidomide and must either
             commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
             methods of birth control, one highly effective method (11.8) and one additional
             effective method AT THE SAME TIME, at least 28 days before she starts taking
             lenalidomide through 90 days and ibrutinib through 30 days after the last dose of
             study drug. FCBP must also agree to ongoing pregnancy testing.

         17. All patients must be registered in and must comply with all requirements of the
             Revlimid Rems™ program.

        Exclusion Criteria:

          1. Any serious medical condition that, in the investigator opinion, places the patient at
             unacceptable risk and/or would prevent the subject from signing the informed consent
             form. Examples include but are not limited to, uncontrolled hypertension, uncontrolled
             diabetes mellitus, active/symptomatic coronary artery disease, active infection
             requiring treatment with intravenous (IV) antibiotics, antiviral or antifungal agents,
             active hemorrhage, or psychiatric illness in the investigator's opinion places the
             patient at unacceptable risk and would prevent the subject from signing the informed
             consent form.

          2. Pregnant or breastfeeding females.

          3. Known human immunodeficiency virus (HIV) infection. Patients with active hepatitis B
             infection (not including patients with prior hepatitis B vaccination; or positive
             serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there
             is no active disease. These patients should be optimized by GI consultation for
             Hepatitis B and Infectious Disease consult for Hepatitis C.

          4. The patient has a prior or concurrent malignancy that in the opinion of the
             investigator, presents a greater risk to the patient's health and survival, than of
             the MCL, within the subsequent 6 months at the time of consent.

          5. History of stroke or intracranial hemorrhage within 6 months prior to signing the
             consent

          6. Patients at high-risk for thromboembolic disease, such as those with prior heterotopic
             ossification (h/o) deep venous thrombosis (DVT).

          7. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure or myocardial infarction within 6 months at the
             time of consent or any Class 3 (moderate) or 4 (severe) cardiac disease defined by the
             New York Heart Association Classification

          8. Significant screening electrocardiogram (ECG) abnormalities including left bundle
             branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block,
             bradycardia (< 50bpm), or QTc >500 msec.

          9. Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.

         10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel or ulcerative colitis, symptomatic
             inflammatory bowel disease, or partial or complete bowel obstruction.

         11. Major surgery or wound that has not fully healed within 4 weeks or vaccination with
             live attenuated vaccines within 4 weeks of the first dose of study drugs.

         12. Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist.

         13. Requires treatment with strong Cytochrome P4503A (CYP3A) inhibitors.

         14. All patients with central nervous system lymphoma.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:66 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) at 4 Months of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed Mantle Cell Lymphoma (MCL)
Time Frame:4 months
Safety Issue:
Description:Response assessed according to the International Workshop Standardization Response Criteria for Non-Hodgkin's Lymphoma (Cheson, 2014)

Secondary Outcome Measures

Measure:Summary of Adverse Events of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed Mantle Cell Lymphoma (MCL)
Time Frame:After 1 cycle, 28 days
Safety Issue:
Description:Adverse events assessed according to the Common Toxicity Criteria for Adverse Events version 4.03. (CTCAE v4.03)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Hematopoietic/Lymphoid Cancer
  • Mantle Cell Lymphoma
  • MCL
  • Newly-diagnosed
  • Ibrutinib
  • PCI-32765
  • Imbruvica
  • Rituximab
  • Rituxan
  • Lenalidomide
  • CC-5013
  • Revlimid
  • Dexamethasone
  • Decadron

Last Updated

September 5, 2017