The primary objective of the study is to establish a pharmacologically active dose of mavorixafor in combination with ibrutinib based on pooled safety, clinical response, pharmacokinetic (PK) and pharmacodynamic (PD) data to select the recommended dose for a randomized registrations trial.
This is an intrapatient dose-escalation study. Three dose levels of mavorixafor will be explored: 200 milligrams (mg) once daily (QD) (dose level 1), 400 mg QD (dose level 2), and 600 mg QD (dose level 3). Ibrutinib will be administered at its labeled dose for participants with WM, 420 mg orally QD. Each treatment cycle will be 28 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Mavorixafor capsules will be administered per dose and schedule specified in the arm.
Ibrutinib capsules will be administered per dose and schedule specified in the arm.
Colorado Blood Cancer Institute
Denver, Colorado, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mass General Hospital Cancer Center
Boston, Massachusetts, United States
MD Anderson Cancer Center
Houston, Texas, United States
Number of Participants With DLTs
Time frame: Cycle 1 (28 days)
Percent Change From Baseline in Immunoglobulin M (IgM) at Cycle 1
Time frame: Baseline, at the end of Cycle 1 (cycle length = 28 days)
Percent Change From Baseline in IgM at Cycle 2
Time frame: Baseline, at the end of Cycle 2 (cycle length = 28 days)
Percent Change From Baseline in IgM at Cycle 3
Time frame: Baseline, at the end of Cycle 3 (cycle length = 28 days)
Percent Change From Baseline in Hemoglobin (Hgb) at Cycle 1
Time frame: Baseline, at the end of Cycle 1 (cycle length = 28 days)
Percent Change From Baseline in Hgb at Cycle 2
Time frame: Baseline, at the end of Cycle 2 (cycle length = 28 days)
Percent Change From Baseline in Hgb at Cycle 3
Time frame: Baseline, at the end of Cycle 3 (cycle length = 28 days)
Maximum Observed Plasma Concentration (Cmax) of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Cmax of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Time to Reach Cmax (Tmax) of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
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University of Athens
Athens, Greece
Tmax of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Half-Life (t1/2) of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
t1/2 of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Accumulation Ratio of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Accumulation Ratio of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Area Under the Concentration-Time Curve (AUC) of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
AUC of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Clearance of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Clearance of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Volume of Distribution (Vd) of Mavorixafor
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Vd of Ibrutinib
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 8 to 10 hours post-dose on Day 1 and Day 21 of Cycle 1, 2, and 3 (each cycle length = 28 days)
Change From Baseline in AUC of Absolute Neutrophil Count (ANC) at Cycle 1
Time frame: Baseline, at the end of Cycle 1 (cycle length = 28 days)
Change From Baseline in AUC of ANC at Cycle 2
Time frame: Baseline, at the end of Cycle 2 (cycle length = 28 days)
Change From Baseline in AUC of ANC at Cycle 3
Time frame: Baseline, at the end of Cycle 3 (cycle length = 28 days)
Maximal Change From Baseline in ANC Count at Cycle 1
Time frame: Baseline, at the end of Cycle 1 (cycle length = 28 days)
Maximal Change From Baseline in ANC Count at Cycle 2
Time frame: Baseline, at the end of Cycle 2 (cycle length = 28 days)
Maximal Change From Baseline in ANC Count at Cycle 3
Time frame: Baseline, at the end of Cycle 3 (cycle length = 28 days)
Percent Change From Baseline in Serum IgM Levels Over the Time
Time frame: Baseline, at each cycle throughout the study (up to approximately 2 years) (cycle length = 28 days)
Change From Baseline in Hgb at Over the Time
Time frame: Baseline, at each cycle throughout the study (up to approximately 2 years) (cycle length = 28 days)
Major Response Rate
Major response rate is defined as percentage of participants with complete response + very good partial response + partial response.
Time frame: From Baseline up to end of study (up to approximately 2 years)
Number of Participants With Adverse Events (AEs)
Time frame: From Baseline up to end of study (up to approximately 2 years)