Page 11 - Deleware Medical Journal - September/October 2019

A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)
The objectives of the trial are:
Primary Objective:
To compare the progression-free survival (PFS) between control treatment and experimental treatment strategies: ibrutinib/obinutuzumab (IO) with ibrutinib maintenance (IM) versus ibrutinib / venetoclax / obinutuzumab (IVO) regardless of IM or observation.
Secondary Objective:
• To compare BM (bone marrow) MRD (minimal residual disease)- complete remission (CR) rates and depth of response at Cycle 15 Day 1 between
patients treated with IO versus IVO.
• To compare overall survival (OS) between the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation. • To compare the 5-year PFS and OS for the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation.
• To describe the toxicity profile for each of the treatment strategies and by each treatment course.
Correlative Science Objective:
To compare MRD status between blood and bone marrow at the end of induction treatment/Cycle 15 Day 1 to determine whether blood MRD can be
used as a surrogate to bone marrow MRD with these treatment regimens.
Eligibility:
Pre-registration Eligibility Criteria: Step 0
CLL diagnosis & Central FISH blood submission
Re-registration Eligibility Criteria: Step 2
• Completion of first 14 cycles of therapy and remain on ibrutinib
• Receipt of central BM MRD results and completion of response evaluation
Treatment: Registration: Step 1
Arm 1: Ibrutinib 420 mg PO daily days 1-28 for 15 cycles; Obinutuzumab 100 mg IV 100 mg on C1D1, 900 mg on C1D2, 1000 mg on Cycle1D8 & C1D15, C2-6D1
Arm 2: Same as Arm 1 + Venetoclax 20 mg daily PO beginning C3D1, dose escalated weekly to a final dose of 400 mg on C4D1, then 400 mg daily PO C4D1-C14D28
C15D1 Response Assessment Specimen submission for central BM MRD & local response assessment & labs performed. At the same time, continue Ibrutinib 420 mg PO daily C15D1-D28.
Re-Register: Step 2
Arm 1: Ibrutinib 420 mg PO daily days 1-28 until progression or unacceptable adverse events
Arm 2: Any response except BM MRD- CR (BM MRD+ CR, PR, PRL, SD): Ibrutinib 420 mg PO daily days 1-28 until progression or unacceptable adverse events
Arm 2: BM MRD – CR: Observation
For information regarding this clinical trial or if you would like to have the list of open protocols emailed to you, please call the Cancer Research Office at (302) 623-4450 or email akee@christianacare.org.
CANCER CLINICAL TRIAL
Registration Eligibility Criteria: Step 1
• Diagnosis with CLL in accordance with 2018 IWCLL criteria
• Intermediate or high-risk Rai stage CLL
• Criteria met for treatment as defined by 2018 IWCLL guidelines
• No prior therapy for CLL (except palliative steroids or treatment of autoimmune complications)
• Age ≥ 70 years, ECOG performance status 0-2
• No comorbid conditions or other active diseases
• No known allergy to mannitol
• No prior significant hypersensitivity to rituximab
• No major surgery within 10 days or minor surgery within 7 days
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