This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive non-Hodgkin lymphoma, who have not previously received a Bcl-2 or Phosphoinositide 3-kinase (PI3K) inhibitor. The Phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Duvelisib will be taken continuously. This is a defining dose study, therefore the dose of Duvelisib may change.
Venetoclax will be taken continuously. This is a defining dose study, therefore the dose of Venetoclax will change.
Site Reference ID/Investigator# 145677
Tucson, Arizona, United States
Site Reference ID/Investigator# 147922
Chicago, Illinois, United States
Site Reference ID/Investigator# 148562
Harvey, Illinois, United States
Number of participants with adverse events
Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.
Time frame: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose
Maximum observed plasma concentration (Cmax) of duvelisib
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Maximum observed plasma concentration (Cmax) of venetoclax
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10, 12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Time to maximum observed plasma concentration (Tmax) of duvelisib
The time at which the maximum plasma concentration (Cmax) is observed.
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Time to maximum observed plasma concentration (Tmax) of venetoclax
The time at which the maximum plasma concentration (Cmax) is observed.
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib
The area under the plasma concentration-time curve over a 12-hour dose interval
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Site Reference ID/Investigator# 148561
Goshen, Indiana, United States
Site Reference ID/Investigator# 145674
Baltimore, Maryland, United States
Site Reference ID/Investigator# 145145
Boston, Massachusetts, United States
Site Reference ID/Investigator# 148010
Detroit, Michigan, United States
Site Reference ID/Investigator# 147747
St Louis, Missouri, United States
Site Reference ID/Investigator# 145146
Lebanon, New Hampshire, United States
Site Reference ID/Investigator# 148559
Greenville, South Carolina, United States
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
The area under the plasma concentration-time curve over a 24-hour dose interval
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax
Time frame: Minimum first cycle of dosing (28 days)
Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib
Time frame: Minimum first cycle of dosing (28 days)
Progression-free survival (PFS)
Progression-free survival will be defined as the number of days from the date of study drug start to the date of documented disease progression, relapse of death due to any cause whichever occurs first.
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Overall Response Rate (ORR)
Overall response rate will be defined as the proportion of participants who achieve a partial remission or better.
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Time to Tumor Progression (TTP)
Time to tumor progression is defined as the number of days from the date of study drug start to the date of the first documented disease progression or relapse.
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Duration of Response (DOR)
Duration of response is defined as the number of days from the date of documented first response of partial remission or better to the date of documented disease progression/relapse or death due to the disease whichever occurs first
Time frame: Measured up to 2 years after the last participant has enrolled in the study