Trial Outcomes & Findings for Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (NCT NCT04209621)

NCT ID: NCT04209621

Last Updated: 2022-03-09

Results Overview

Overall response rate with modification for treatment-related lymphocytosis. Response is defined below and followed iwCLL 2008 guidelines and incorporated clarifications for lymphocytosis associated with kinase inhibitors. Complete Response: Lymph Nodes = None greater or equal to 1.5 cm; Spleen \&/or liver size = Spleen less than 13 cm \&/or liver size normal; Blood Lymphocytes = less than 4000/μL. Partial Response: Lymph Nodes, Spleen and/or liver size, plus Blood Lymphocytes = Decrease greater than or equal to 50%. Partial Remission with Lymphocytosis: Lymph Nodes and Spleen and/or liver size = Decrease greater than or equal to 50%; Blood Lymphocytes = Increase or decrease greater than 50%. Progressive Disease: Lymph Nodes = Increase ≥ 50% or any new lesion \> 1.5 cm; Spleen and/or liver size = Increase ≥ 50% or new splenomegaly; Blood Lymphocytes = Increase ≥ 50% and \> 5000/μL B cells. Stable Disease: Lymph Nodes, Spleen and/or liver size plus Blood Lymphocytes =Change of -49% to +49%

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

After 12 weeks

Results posted on

2022-03-09

Participant Flow

Study was terminated prematurely due to unexpected sudden death on study.

Participants were enrolled on study based on safety lead-in with a 3+3 dose-escalation design.

Participant milestones

Participant milestones
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Overall Study STARTED	3
Overall Study Dose Level 1	3
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Overall Study Death	1
Overall Study Study Terminated Early	2

Baseline Characteristics

Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants
Sex: Female, Male Female	1 Participants n=93 Participants
Sex: Female, Male Male	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	2 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	3 participants n=93 Participants

PRIMARY outcome

Timeframe: After 12 weeks

Population: Intent-to-treat population.

Outcome measures

Outcome measures
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Participant Overall Response Rate (ORR) Complete Remission (CR)	0 Participants
Participant Overall Response Rate (ORR) Partial Remission (PR)	0 Participants
Participant Overall Response Rate (ORR) Partial Remission with lymphocytosis (PRL)	0 Participants
Participant Overall Response Rate (ORR) Progressive Disease (PD)	0 Participants
Participant Overall Response Rate (ORR) Stable Disease (SD)	1 Participants

SECONDARY outcome

Timeframe: From Day 1 to progression of disease or death from any cause, which ever came first, assessed up to approximately 6 months

Population: Intent-to-treat population

Number of participants with progression-free survival as defined as time from treatment initiation to progression of disease or death from any cause.

Outcome measures

Outcome measures
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Number of Participants With Progression-free Survival Progression of Disease	1 Participants
Number of Participants With Progression-free Survival Death	1 Participants

SECONDARY outcome

Timeframe: From Day 1 to death from any cause, which ever came first, assessed up to approximately 6 months

Population: Intent-to-treat population

Participant overall survival as defined as time from treatment initiation to death from any cause

Outcome measures

Outcome measures
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Participant Overall Survival Death	1 Participants
Participant Overall Survival Alive	2 Participants

SECONDARY outcome

Timeframe: From initial response [12 weeks or later] to progression of disease

Population: Participants who have achieved response only

Duration of response in days as defined as time from initial response to progression of disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After greater than or equal to 3 cycles [12 weeks] of treatment, up to 6 months

Population: Participants who have had greater than or equal to one response assessment.

Number of participants who achieved best response \[complete response is better than partial response is better than stable disease\]. Complete Response: Lymph Nodes = None greater or equal to 1.5 cm; Spleen \&/or liver size = Spleen less than 13 cm \&/or liver size normal; Blood Lymphocytes = less than 4000/μL. Partial Response: Lymph Nodes, Spleen and/or liver size, plus Blood Lymphocytes = Decrease greater than or equal to 50%. Partial Remission with Lymphocytosis: Lymph Nodes and Spleen and/or liver size = Decrease greater than or equal to 50%; Blood Lymphocytes = Increase or decrease greater than 50%. Progressive Disease: Lymph Nodes = Increase ≥ 50% or any new lesion \> 1.5 cm; Spleen and/or liver size = Increase ≥ 50% or new splenomegaly; Blood Lymphocytes = Increase ≥ 50% and \> 5000/μL B cells. Stable Disease: Lymph Nodes, Spleen and/or liver size plus Blood Lymphocytes =Change of -49% to +49%

Outcome measures

Outcome measures
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=1 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Number of Participants Who Achieved Best Response	0 Participants

SECONDARY outcome

Timeframe: From time of informed consent to 30 days after last dose of duvelisib plus ibrutinib combination

Population: Intent-to-treat population

Safety as defined by number of dose limiting toxicities during first cycle of duvelisib plus ibrutinib combination and serious adverse events while participants are taking duvelisib plus ibrutinib combination followed by duvelisib monotherapy.

Outcome measures

Outcome measures
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 Participants Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Safety of Duvelisib Plus Ibrutinib Combination and Duvelisib Monotherapy	2 Number of Serious Adverse Events

Adverse Events

Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious events: 2 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 participants at risk Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Gastrointestinal disorders Colitis	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.
General disorders Sudden Death Not Otherwise Specified (NOS)	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.

Other adverse events

Other adverse events
Measure	Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma n=3 participants at risk Duvelisib with ibrutinib will be administered for the first six 28-day (± 7) cycles followed by duvelisib alone until disease progression or intolerance. Duvelisib is an orally administered at 15 mg twice a day (dose level 1) or 25 mg twice day (dose level 2). Subjects will continue the same dose of ibrutinib prior to study enrollment for the first six 28-day cycles. Ibrutinib is an orally administered and provided as 140 mg white opaque capsules or tablets in 4 strengths: 140 mg, 280 mg, 420 mg, and 560 mg.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.
Cardiac disorders Sinus tachycardia	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.
Cardiac disorders Ventricular arrhythmia	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • 6 months All events whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded in the patient's medical record.

Additional Information

Sun, Clare, M.D. Principal Investigator, NIH, NHLBI

National Institutes of Health (NIH) / The National Heart, Lung, and Blood Institute (NHLBI)

Phone: 301.402.1806

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place