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Ibrutinib and Obinutuzumab With or Without Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia (EA9161)
Overall Recruitment Status: Active, enrollment completed
 
Official Title
A Randomized Phase III Study of the Addition of Venetoclax to Ibrutinib and Obinutuzumab Versus Ibrutinib and Obinutuzumab in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)
 
Region Sponsors
Northwest
National Cancer Institute (NCI)
 
Acronym KP IRB No.
1454894
 
Study Type Phase
Clinical Trial Phase III
 
Study Population Description
(Adult, Older Adult) Male and Female with confirmed diagnosis of Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
 
Purpose
This phase III trial studies how well ibrutinib and obinutuzumab with or without venetoclax work in treating patients with chronic lymphocytic leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, 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 venetoclax, 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, obinutuzumab, and venetoclax may work better than giving ibrutinib and obinutuzumab in treating patients with chronic lymphocytic leukemia.
 
Detailed Description
PRIMARY OBJECTIVE: To compare the progression free survival (PFS) of the time limited administration of the three-drug combination ibrutinib-obinutuzumab-venetoclax (IOV) to ibrutinib-obinutuzumab (IO) in untreated chronic lymphocytic leukemia (CLL) patients younger than 70 years of age. SECONDARY OBJECTIVES: (1) Evaluate overall survival (OS) of patients based on treatment arm. (2) Monitor and assess toxicity of treatment based on treatment arm. (3) Compare minimal residual disease (MRD) status as assessed by flow cytometry at baseline and then sequentially during treatment of the two treatment arms. (4) Collect baseline and response evaluation (after cycle 19) bone marrow and paired blood specimens for evaluation of MRD. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive ibrutinib orally (PO) daily on days 1-28 and obinutuzumab intravenously (IV) over 4 hours on days 1, 2, 8, and 15 of course 1 and on day 1 of courses 2-6. Patients also receive venetoclax PO once daily (QD) on days 1-28 of courses 3-14. Treatment repeats every 28 days for up to 19 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive ibrutinib PO and obinutuzumab as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients, including those who discontinue therapy early, are followed for response until disease progression, even if non-protocol therapy is initiated. Patients are then followed every 3 months for first 2 years, every 6 months for years 3-5, and then every 12 months for years 6-10. All patients must also be followed through completion of all protocol therapy.
 
Gender Age Limit
Male & Female 18 - 69 years
 
Inclusion Criteria
  • Diagnosis of CLL according to the National Cancer Institute (NCI)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria. This includes previous documentation of: Biopsy-proven small lymphocytic lymphoma OR Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following: Peripheral blood lymphocyte count of greater than 5 x10^9/L, Immunophenotype consistent with CLL defined as: The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc). Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression). Negative fluorescent in situ hybridization (FISH) analysis for t(11,14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
  • No prior chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal anti-body therapy for treatment of CLL or SLL
  • Has met at least one of the following indications for treatment: Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] = <11 g/dl) and/or thrombocytopenia (platelets = <100 x 10^9/L). Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
  • Please contact study team for additional inclusion criteria
 
Exclusion Criteria
  • Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure
  • History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
  • Recent infections requiring systemic treatment
  • need to have completed anti-biotic therapy = >14 days before the first dose of study drug
  • Cerebral vascular accident or intracranial bleed within the last 6 months
  • Infection with known chronic, active hepatitis C
  • Positive serology for hepatitis B defined as a positive test for hepatitis B surface antigen (HBsAg), in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a hepatitis B deoxyribonucleic acid (DNA) test will be performed and, if positive the subject will be ineligible, if the hepatitis (Hep) B DNA test is negative (i.e. viral load undetectable) then the individual is eligible, if a patient who is HBsAg negative, HBcAb positive, and Hep B DNA negative is enrolled, they should be considered for either prophylactic anti-viral therapy (J Clin Oncol. 2013 Aug 1,31(22):2765-72) or careful monitoring for Hep B reactivation (J Clin Oncol. 2014 Nov 20,32(33):3736-43)
  • Please contact study team for additional exclusion criteria

 
Keywords and/or Specific Medical Conditions
  • Leukemia
  • Lymphatic Diseases
  • Antineoplastic Agents
  • Lymphoproliferative Disorders
  • Antineoplastic Agents, Immunological
  • Neoplasms
  • Immune System Diseases
  • Neoplasms by Histologic Type
  • Immunoproliferative Disorders
  • Obinutuzumab
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Venetoclax
  • Leukemia, Lymphoid
  • Oncology (Adult)
 
KP Clinical Facility
  • Central Interstate Medical Office
  • Sunnyside Medical Center
 
Clinical Area
  • Oncology (Adult)


Principal Investigator:
Abdul Hai Mansoor, MD
Contact Information:
- Rhonda Stephenson, RN
-503-335-6310
-rhonda.stephenson@kpchr.org
-Sunnyside Medical Center


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