Clinical Trials /

Ibrutinib in Treating Participants With Newly Diagnosed Low-Risk Mantle Cell Lymphoma

NCT03282396

Description:

This phase II trial studies how well ibrutinib works in treating participants with newly diagnosed low-risk mantle cell lymphoma. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib in Newly Diagnosed Mantle Cell Lymphoma With Low-Risk Disease
  • Official Title: A Phase II Trial of Ibrutinib in Newly Diagnosed Mantle Cell Lymphoma With Low-Risk Disease

Clinical Trial IDs

  • ORG STUDY ID: 2016-0914
  • NCT ID: NCT03282396

Conditions

  • Hematopoietic/Lymphoid Cancer
  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
IbrutinibPCI-32765, ImbruvicaIbrutinib

Purpose

The goal of this clinical research study is to learn if ibrutinib can help to control mantle cell lymphoma (MCL). The safety of this drug will also be studied.

Detailed Description

      Study Drug Administration:

      Each study cycle is 28 days.

      If participant is found to be eligible to take part in this study, participant will take
      ibrutinib by mouth 1 time per day at the same time every day with 1 cup (about 8 ounces) of
      water.

      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 take participant's next dose at participant's usual time the next day.

      Participant should return any unused study drug to all study visits.

      Study Visits:

      On Days 1, 8, 15, and 22 of Cycle 1, participant's vital signs will be taken.

      On Day 1 of every cycle:

        -  Participant will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If participant can become
           pregnant, this blood will also be used for a pregnancy test.

        -  Blood (about 2 teaspoons) will be drawn for biomarker testing. (Cycles 3 and 7 only)

      On Day 1 of Cycle 3 and Cycle 7:

        -  Blood (about 2 teaspoons) will be drawn for biomarker testing.

        -  Participant will have a bone marrow biopsy and aspirate for biomarker testing.

      Every other cycle starting in Cycle 3 and up to Cycle 8 (Cycles 3, 5, and 7) and then every 4
      cycles after that starting in Cycle 9 (Cycles 9, 13, 17, and 21), participant will have a CT
      scan to check the status of the disease.

      At any time your doctor thinks it is needed, participant may have any of the following
      procedures to check the status of the disease:

        -  PET/CT scan

        -  bone marrow biopsy

        -  colonoscopy/GI endoscopy with a core biopsy

      If participant can become pregnant, and the doctor thinks it is needed, blood (about 1
      teaspoon) or urine will be collected for a pregnancy test at any time while participant is on
      study.

      Length of Study:

      Participant may continue taking the study drug for up to 3 years. Participant will no longer
      be able to take the study drug if the disease gets worse, if intolerable side effects occur,
      or if participant is unable to follow study directions.

      Participation on the study will be over after the last follow-up phone call.

      End-of-Treatment Visit:

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

        -  Participant will have a physical exam.

        -  Participant will have an EKG.

        -  Blood (about 2 teaspoons) will be drawn for routine tests and to check the status of the
           disease. If participant is able to become pregnant, this blood sample will also be used
           for a pregnancy test.

        -  Participant will have a PET/CT scan and chest x-ray to check the status of the disease.

        -  If the doctor thinks it is needed, participant may have an endoscopy with a biopsy; a
           colonoscopy with a biopsy; and/or a bone marrow biopsy.

      Long Term Follow Up Period:

      Every 2 months for the first 6 months after the End-of-Treatment visit, then every 2-4 months
      for 2 years, and then 4-6 months after 2 years, a member of the study staff will call
      participant to ask about participant's health. These phone calls will take about 5 minutes
      each time.

      Participant's study data and results may be used by Pharmacyclics, its affiliates and its
      collaborators (such as Janssen Biotech, Inc.) for research related to cancer.

      This is an investigational study. Ibrutinib is FDA approved and commercially available for
      the treatment of several types of cancer. Its use in treating MCL is investigational. The
      study doctor can explain how the study drug is designed to work.

      Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
IbrutinibExperimentalParticipants receive Ibrutinib by mouth 1 time per day in a 28 day cycle. Participants called by study staff every 2 months for the first 6 months after the End-of-Treatment visit, then every 2-4 months for 2 years, and then 4-6 months after 2 years.
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.
             Patients must have never received any prior therapy for their disease. Patients have
             been observed for 3 - 6 months with no progression as per imaging assessments.

          2. Low risk disease (without the following risk factors: Blastoid variant histology,
             Pleomorphic variant histology, Ki-67 >/= 50%, High-risk MCL International Prognostic
             Index (MIPI), Bulky tumors >3 cm, Presence of B symptoms)

          3. Understand and voluntarily sign an institutional review board (IRB)-approved informed
             consent form.

          4. Age >/= 18 years at the time of signing the informed consent.

          5. Patients should in general have bi-dimensional measurable disease with their biggest
             tumor less than or equal to 3 cm. [bone marrow or gastrointestinal (GI) only
             involvement is acceptable].

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

          7. Absolute neutrophil count (ANC) > 1000/mm^3, platelet count >100,000/mm^3. Patients
             who have bone marrow infiltration by MCL are eligible if their ANC is >/= than 500 or
             their platelet level is >/= than 50,000 /mm^3. Platelet transfusions are allowed.

          8. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
             alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 3 x upper
             limit of normal or < 5 x upper limit of normal if hepatic metastases are present.
             Serum bilirubin <1.5 mg/dl and creatinine (Cr) Clearance >/= 30 mL/min.

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

         10. Willing and able to participate in all study related procedures and therapy including
             swallowing capsules without difficulty and having a screening core biopsy.

         11. Female subjects who are of non-reproductive potential (ie, post-menopausal by history
             - no menses for >/= 1 year; OR history of hysterectomy; OR history of bilateral tubal
             ligation; OR history of bilateral oophorectomy). Female subjects of childbearing
             potential must have a negative serum pregnancy test upon study entry.

         12. Male and female subjects who agree to use highly effective methods of birth control
             (eg, implants, injectables, combined oral contraceptives, some intrauterine devices
             [IUDs], sexual abstinence, or sterilized partner) and a barrier method (eg., condoms,
             vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last
             dose of study drug for females and 90 days for males.

        Exclusion Criteria:

          1. Any serious medical condition including but not limited to uncontrolled hypertension,
             diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive
             pulmonary disease (COPD), renal failure, splenomegaly, leukemic features, active
             hemorrhage, or psychiatric illness that, 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 history of human immunodeficiency virus (HIV) or active with hepatitis C virus
             (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core
             antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative
             polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive
             will be excluded.

          4. All patients with history of central nervous system lymphoma.

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

          6. 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.

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

          8. Unable to swallow capsules, 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.

          9. Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist,
             active treatment for pulmonary embolism (PE)/ deep vein thrombosis (DVT) and persons
             with mechanical cardiac valves.

         10. Requires treatment with strong CYP3A4/5 inhibitors.
             http://medicine.iupui.edu/clinpharm/ddis/table.aspx

         11. Patients with blastoid and pleomorphic variants.

         12. Ki-67 to be equal or more than 50%.

         13. Patients with bi-dimensional measurable disease with a tumor >/= 3 cm.

         14. Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification

         15. Any uncontrolled active systemic infection

         16. Major surgery within 4 weeks of first dose of study drug.

         17. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.

         18. Recent infection requiring systemic treatment that was completed </= 14 days before
             the first dose of study drug.

         19. Known bleeding disorders (eg, von Willebrand's disease or hemophilia).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) of Ibrutinib in Newly-Diagnosed Participants with Low-Risk Mantle Cell Lymphoma (MCL)
Time Frame:3 years
Safety Issue:
Description:International Workshop Standardized Response Criteria for non-Hodgkin's Lymphoma used to measure PFS.

Secondary Outcome Measures

Measure:Adverse Events of Ibrutinib in Newly-Diagnosed Participants with Low-Risk Mantle Cell Lymphoma (MCL)
Time Frame:3 years
Safety Issue:
Description:Adverse events assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03.

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

Last Updated

September 13, 2017