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Ibrutinib Versus Ibrutinib + Rituximab (i vs iR) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02007044
First Posted: December 10, 2013
Last Update Posted: October 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

You are being asked to take part in this study because you have chronic lymphocytic leukemia (CLL) with a chromosomal abnormality (17p/TP53 deletion) or CLL that has come back after treatment.

The goal of this clinical research study is to learn if the combination of ibrutinib and rituximab can help to control CLL better than ibrutinib alone. The safety of these treatments will be also studied.


Condition Intervention Phase
Leukemia Drug: Ibrutinib Drug: Rituximab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Study of Ibrutinib Versus Ibrutinib Plus Rituximab (i Versus iR) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression-Free survival (PFS) Rate [ Time Frame: 2 years ]
    Progression-free survival (PFS) time is defined as the time from start of treatment to progression or death date. Progression events can be progressive lymphadenopathy, progressive lymphocytosis, progressive cytopenias, or Richter's transformation, as defined in the 2008 IWCLL guidelines22.


Enrollment: 209
Actual Study Start Date: December 6, 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibrutinib (Subgroup 1)
Ibrutinib started on Day 1 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.
Drug: Ibrutinib

Ibrutinib Subgroup 1 started on Day 1 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Ibrutinib Subgroup 2 started on Day 2 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Other Name: PCI-32765
Experimental: Ibrutinib (Subgroup 2)
Ibrutinib started on Day 2 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.
Drug: Ibrutinib

Ibrutinib Subgroup 1 started on Day 1 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Ibrutinib Subgroup 2 started on Day 2 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Other Name: PCI-32765
Experimental: Ibrutinib (Subgroup 1) + Rituximab

Ibrutinib 420 mg (3 x 140-mg capsules) given orally on Day 1 of cycle 1 for each 28 day cycle. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Rituximab 375 mg/m2 given intravenously on Day 1, Day 8, Day 15, and Day 22 , and then continued once every 4 weeks only on Days 1 during cycles 2 - 6. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Drug: Ibrutinib

Ibrutinib Subgroup 1 started on Day 1 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Ibrutinib Subgroup 2 started on Day 2 of cycle 1 at dose of 420 mg (3 x 140-mg capsules) orally once daily in each 28 day cycle.

Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Other Name: PCI-32765
Drug: Rituximab
Rituximab 375 mg/m2 given intravenously on Day 1, Day 8, Day 15, and Day 22 , and then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
Other Name: Rituxan
Experimental: Ibrutinib (Subgroup 2) + Rituximab

Ibrutinib 420 mg (3 x 140-mg capsules) given orally on Day 2 of cycle 1 for each 28 day cycle. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Rituximab 375 mg/m2 given intravenously on Day 1, Day 8, Day 15, and Day 22 , and then continued once every 4 weeks only on Days 1 during cycles 2 - 6. Patients in the iR group alternatingly assigned to subgroups 1 and 2, the purpose is to compare rituximab infusion reactions.

Drug: Rituximab
Rituximab 375 mg/m2 given intravenously on Day 1, Day 8, Day 15, and Day 22 , and then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
Other Name: Rituxan

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a diagnosis CLL/SLL or Prolymphocytic Leukemia (PLL) and be previously treated. Given the poor outcome of CLL/SLL/PLL patients with 17p del or TP53 mutation to standard frontline chemo-immunotherapy, such patients will be eligible if they are untreated.
  2. Patients must have an indication for treatment by 2008 IWCLL Criteria.
  3. Patients must be age >/= 18 years at the time of signing informed consent, understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations.
  4. ECOG performance status of 0-2.
  5. Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.
  6. Adequate renal and hepatic 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 who will be allowed to participate; an ALT </=2.5 x ULN; and an estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft- Gault equation unless disease related.
  7. Free of prior malignancies for 3 years with exception of patients diagnosed with basal cell or 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 have been treated and/or diagnosed in the past 3 years prior to study enrolment. If patients have another malignancy that was treated within the last 3 years, such patients can be enrolled, after consultation with the Principal Investigator, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center.
  8. A Urine Pregnancy Test (within 7 days of enrollment date) is required for women with childbearing potential.

Exclusion Criteria:

  1. Pregnant or breast-feeding females.
  2. Prior therapy with ibrutinib or other kinase inhibitors that target Bruton's tyrosine kinase (BTK). Patients who previously received therapy with the PI3K delta inhibitor idelalisib (Zydelig) are allowed to be enrolled.
  3. Treatment including chemotherapy, chemo-immunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg Prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial.
  4. Investigational agent received within 30 days prior to the first dose of study drug.
  5. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  6. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
  7. Patients with severe hematopoietic insufficiency, as defined by an absolute neutrophil count of less than 500/MuL, unless disease-related, and/or a platelet count of less than 30,000/MuL at time of screening for this protocol.
  8. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with ibrutinib and rituximab.
  9. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
  10. History of stroke or cerebral hemorrhage within 6 months.
  11. Evidence of bleeding diathesis or coagulopathy within 3 months.
  12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment date, anticipation of need for major surgical procedure during the course of the study.
  13. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to enrollment date. Bone marrow aspiration and/or biopsy are allowed.
  14. Serious, non-healing wound, ulcer, or bone fracture.
  15. Treatment with Coumadin. Patients who recently received Coumadin must be off Coumadin for at least 7 days prior to start of the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02007044


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pharmacyclics LLC.
Investigators
Principal Investigator: Jan A. Burger, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02007044     History of Changes
Other Study ID Numbers: 2013-0703
NCI-2014-00989 ( Registry Identifier: NCI CTRP )
First Submitted: December 5, 2013
First Posted: December 10, 2013
Last Update Posted: October 20, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic lymphocytic leukemia
CLL
Relapsed
Ibrutinib
PCI-32765
Rituximab
Rituxan

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents