Clinical Trials /

Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)

NCT03207555

Description:

The standard approach to managing chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) is to wait until you have symptoms before treatment is given. The goal of this clinical research study is to learn if providing earlier treatment for CLL or SLL with ibrutinib in patients who do not have symptoms will be more effective than waiting until symptoms develop. This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of patients with CLL or SLL. It is considered investigational to give ibrutinib to CLL and SLL patients before symptoms develop. The study doctor can describe how the study drug is designed to work. Up to 50 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)
  • Official Title: Ibrutinib Monotherapy in Early Stage Chronic Lymphocytic Leukemia (CLL) Without IWCLL/NCI-WG 2008 Treatment Indications But With High-Risk Features for Disease Progression

Clinical Trial IDs

  • ORG STUDY ID: 2017-0039
  • SECONDARY ID: NCI-2018-01121
  • NCT ID: NCT03207555

Conditions

  • Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia

Interventions

DrugSynonymsArms
IbrutinibPCI-32765, ImbruvicaIbrutinib

Purpose

The standard approach to managing chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) is to wait until you have symptoms before treatment is given. The goal of this clinical research study is to learn if providing earlier treatment for CLL or SLL with ibrutinib in patients who do not have symptoms will be more effective than waiting until symptoms develop. This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of patients with CLL or SLL. It is considered investigational to give ibrutinib to CLL and SLL patients before symptoms develop. The study doctor can describe how the study drug is designed to work. Up to 50 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Drug Administration:

      If you are found to be eligible to take part in this study, you will take ibrutinib by mouth
      1 time every day. Each dose should be taken with about 1 cup (8 ounces) of water.

      If you miss a dose of ibrutinib, it can be taken as soon as possible on the same day. You
      should take your next dose as scheduled. If you forget to take a dose, do not take extra
      capsules on the next day to "make up" the missed dose.

      You will be given standard drugs, such as allopurinol or valacyclovir, to help decrease the
      risk of side effects. You may ask the study staff for information about how the drugs are
      given and their risks. If you have side effects, your dose of ibrutinib may be lowered or
      temporarily stopped until you recover from the side effects.

      Length of Treatment:

      You may take ibrutinib for up to 2 years (24 cycles). If at the end of 2 years you are
      benefitting from ibrutinib and the study doctor thinks it is in your best interest to
      continue taking it, other treatment options will be discussed with you to allow you to
      continue to take ibrutinib.

      You will no longer be able to take the study drug if the disease gets worse, if intolerable
      side effects occur, or if you are unable to follow study directions.

      Study Visits:

      Each cycle is 28 days.

      On Day 28 of Cycles 1-3 and then every 3 cycles after that until Cycle 24 (Cycles 6, 9, 12,
      and so on):

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

        -  You will have a physical exam.

        -  You will have an EKG.

      On Day 28 of Cycles 1, 3, 6, 12, and 24, blood (about 3 tablespoons) will be drawn to test
      for genetic mutations related to the disease. At Months 3, 6, and 12, additional blood (about
      8 teaspoons) will be drawn for immune system testing.

      On Day 28 of Cycles 6, 12, 18 and 24, you will have CT, MRI or PET/CT scan to check the
      status of the disease. Depending on the results of the CT, MRI or PET/CT scans, you may not
      need to have these scans repeated. The doctor will discuss this with you.

      On Day 28 of Cycles 6, 12 and 24, you will have a bone marrow biopsy to check the status of
      the disease.

      If the doctor thinks it is needed or if the disease gets worse, some tests/procedures, such
      as physical exams and blood draws for routine tests, may be repeated more often.

      Long-term follow-up:

      Every 3 months, during a regularly scheduled clinic visit (if you are still receiving care at
      MD Anderson) or by phone (if you are receiving care outside of MD Anderson), you will be
      asked how you are doing, if you are still taking ibrutinib, and if you have any side effects.
      If called, this call should last about 5-10 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
IbrutinibExperimentalParticipants take Ibrutinib by mouth 1 time every day for up to 2 years (24 cycles).
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must be age >/=18 years at the time of informed consent, understand and
             voluntarily sign an informed consent, and be able to comply with study procedures and
             follow-up examinations.

          2. No treatment indication according to IWCLL/NCI-WG (International Working Group in
             Chronic Lymphocytic Leukemia/National Cancer Institute-Working Group) 2008 criteria

          3. Estimated time to first treatment of 3 years or less according to MDACC nomogram

          4. ECOG performance status of 0-2

          5. Male and female subjects who agree to use both a highly effective method of birth
             control (eg, implants, injectables, combined oral contraceptives, some intrauterine
             devices [IUDs], complete 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. OR 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)

          6. Adequate hepatic and renal function as indicated by all of the following: Total
             bilirubin </=1.5 x institutional Upper Limit of Normal (ULN) except for patients with
             bilirubin elevation due to Gilbert's disease or of non-hepatic origin who will be
             allowed to participate, provided bilirubin is </=3 x institutional ULN; an ALT </=2.5
             x ULN; and estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the
             Cockcroft- Gault equation.

          7. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN (unless abnormalities are unrelated to
             coagulopathy or bleeding disorder).

          8. Free of prior malignancies for 3 years with exception of patients diagnosed with basal
             cell or non-metastatic squamous cell carcinoma of the skin, or carcinoma in situ of
             the cervix or breast, who are eligible even if they are currently treated or were
             treated and/or diagnosed in the past 3 years prior to study enrolment

          9. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria

        Exclusion Criteria:

          1. Receipt of any prior therapy for CLL. Patients who have received "early intervention"
             with INVAC-1 vaccine against hTERT will be eligible provided all of the following
             exist: i) They had no response to the vaccine treatment (persistent CLL >1% in bone
             marrow). ii) ≥3 months have elapsed since the last dose of vaccine. iii) No residual
             toxicities attributable to the vaccine exist at the time of study enrollment. iv) The
             patient does not meet IWCLL criteria for requiring treatment.

          2. Richter Transformation

          3. Active malignancy requiring systemic therapy, other than CLL, with the exception of:
             adequately treated in situ carcinoma of the cervix uteri; adequately treated basal
             cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy
             confined and surgically resected (or treated with other modalities) with curative
             intent.

          4. Systemic anticoagulation with warfarin or other Vitamin K antagonists

          5. Active and uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune
             thrombocytopenia (ITP) requiring daily prednisone dose of >/=20 mg

          6. Current and concurrent use of strong CYP3A4 inhibitors or inducers

          7. Pregnant or breast-feeding females

          8. Uncontrolled and active systemic fungal, bacterial, viral, or other infection (defined
             as exhibiting ongoing signs/symptoms related to the infection and without improvement,
             despite appropriate antibiotics or other treatment)

          9. Any other severe concurrent disease, or history of serious organ dysfunction or
             disease involving the heart, kidney, liver or other organ system that, in the
             investigator's opinion, may place the patient at undue risk to undergo therapy with
             ibrutinib

         10. Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
             Association Functional Classification; or a history of myocardial infarction, unstable
             angina, or acute coronary syndrome within 6 months prior to randomization

         11. History of ischemic stroke within 6 months prior to enrollment

         12. Evidence of bleeding diathesis or coagulopathy within 3 months (eg, von Willebrand's
             disease or hemophilia

         13. Any history of symptomatic intracranial hemorrhage

         14. Major surgical procedure with 4 weeks of first dose of study drug; open biopsy, or
             significant traumatic injury within 7 days prior to enrollment date; anticipation of
             need for major surgical procedure during the course of the study

         15. Minor surgical procedures, fine needle aspirations or core biopsies within 3 days
             prior to enrollment date. Bone marrow aspiration and/or biopsy are allowed

         16. Serious, non-healing wound, ulcer, or bone fracture

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

         18. Active, uncontrolled infection

         19. 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

         20. Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification (see Appendix L)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission (CR) with Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)
Time Frame:2 years
Safety Issue:
Description:Response assessed according to the IWCLL/NCI-WG 2008 criteria.

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS) with Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)
Time Frame:2 years
Safety Issue:
Description:Response assessed according to the IWCLL/NCI-WG 2008 criteria.
Measure:Overall response rate (ORR) of Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)
Time Frame:6, 12 and 24 months
Safety Issue:
Description:Response assessed according to the IWCLL/NCI-WG 2008 criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms stated as primary lymphoid haematopoietic
  • Chronic Lymphocytic Leukemia
  • CLL
  • Small Lymphocytic Leukemia
  • SLL
  • Ibrutinib
  • PCI-32765
  • Imbruvica

Last Updated

August 2, 2019