Trial Outcomes & Findings for A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO) (NCT NCT02004522)

NCT ID: NCT02004522

Last Updated: 2023-09-21

Results Overview

The primary efficacy endpoint for the study was PFS, defined as time from randomization to the first documentation of PD as determined by blinded independent review or death due to any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

319 participants

Primary outcome timeframe

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Results posted on

2023-09-21

Participant Flow

Participant milestones

Participant milestones
Measure	Duvelisib Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Overall Study STARTED	160	159
Overall Study Number of Subjects Treated	158	155
Overall Study COMPLETED	34	0
Overall Study NOT COMPLETED	126	159

Reasons for withdrawal

Reasons for withdrawal
Measure	Duvelisib Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Overall Study Adverse Event	55	6
Overall Study Withdrawal by Subject	13	7
Overall Study Death	12	3
Overall Study Physician Decision	3	4
Overall Study Protocol Violation	1	0
Overall Study Other is reason listed by PI	4	1
Overall Study Never Dosed	2	4
Overall Study Disease Progression	35	31
Overall Study Completed Treatment Cycles Per Protocol	1	103

Baseline Characteristics

A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.	Total n=319 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	48 Participants n=99 Participants	54 Participants n=107 Participants	102 Participants n=206 Participants
Age, Categorical >=65 years	112 Participants n=99 Participants	105 Participants n=107 Participants	217 Participants n=206 Participants
Sex: Female, Male Female	64 Participants n=99 Participants	64 Participants n=107 Participants	128 Participants n=206 Participants
Sex: Female, Male Male	96 Participants n=99 Participants	95 Participants n=107 Participants	191 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=99 Participants	7 Participants n=107 Participants	15 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	130 Participants n=99 Participants	133 Participants n=107 Participants	263 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	22 Participants n=99 Participants	19 Participants n=107 Participants	41 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	150 Participants n=99 Participants	142 Participants n=107 Participants	292 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	16 Participants n=107 Participants	25 Participants n=206 Participants
Region of Enrollment New Zealand	6 participants n=99 Participants	6 participants n=107 Participants	12 participants n=206 Participants
Region of Enrollment Austria	3 participants n=99 Participants	8 participants n=107 Participants	11 participants n=206 Participants
Region of Enrollment Belgium	13 participants n=99 Participants	14 participants n=107 Participants	27 participants n=206 Participants
Region of Enrollment Hungary	35 participants n=99 Participants	30 participants n=107 Participants	65 participants n=206 Participants
Region of Enrollment United States	30 participants n=99 Participants	21 participants n=107 Participants	51 participants n=206 Participants
Region of Enrollment Italy	23 participants n=99 Participants	18 participants n=107 Participants	41 participants n=206 Participants
Region of Enrollment United Kingdom	7 participants n=99 Participants	10 participants n=107 Participants	17 participants n=206 Participants
Region of Enrollment Australia	9 participants n=99 Participants	12 participants n=107 Participants	21 participants n=206 Participants
Region of Enrollment France	12 participants n=99 Participants	18 participants n=107 Participants	30 participants n=206 Participants
Region of Enrollment Germany	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Region of Enrollment Spain	21 participants n=99 Participants	19 participants n=107 Participants	40 participants n=206 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Population: Intent to Treat

The primary efficacy endpoint for the study was PFS, defined as time from randomization to the first documentation of PD as determined by blinded independent review or death due to any cause.

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Progression-free Survival (PFS)	13.3 Months Interval 12.1 to 16.8	9.9 Months Interval 9.2 to 11.3

SECONDARY outcome

Timeframe: Until disease progression or unacceptable toxicity assessed up to 6 years

Population: Intent to Treat

ORR is a key secondary efficacy endpoint with overall response defined as best response of CR, CRi, PR, or PRwL, according to the modified IWCLL/IWG Response Criteria, with modification for treatment-related lymphocytosis as defined in the protocol.

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Overall Response Rate (ORR)	118 Participants	72 Participants

SECONDARY outcome

Timeframe: 3 years

Population: Subjects With Abnormal Hematologic Values at Baseline

Subjects with hematologic improvement included those subjects with abnormally high values for neutrophil count, hemoglobin, or platelet count at Baseline determined to have consistently met the criteria of an improvement for those parameters for a period of at least 60 days during which the subject did not have a transfusion or exogenous cytokines.

Outcome measures

Outcome measures
Measure	Duvelisib n=94 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=95 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Number of Subjects With Hematologic Improvements	56 Participants	51 Participants

SECONDARY outcome

Timeframe: Every 6 months for up to 3 years after first dose

Population: Intent to Treat

A stratified Cox regression analysis was used to test for any treatment effect.

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Overall Survival	54.94 Months Interval 43.0 to 67.99	63.25 Months Interval 44.15 to NA = The upper limit of the confidence interval is not estimable because of an insufficient number of events at the time of analysis.

SECONDARY outcome

Timeframe: 3 years

Population: Intent to Treat

Lymph node response defined as greater than or equal to 50% decrease in the SPD of target lymph nodes

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Lymph Node Response Rate	136 Participants	25 Participants

SECONDARY outcome

Timeframe: Time from the first documentation of response to first documentation of progressive disease or death due to any cause

Population: Intent to Treat

Duration of response is defined only for subjects demonstrating a response (eg, CR, CRi, PR, PRwL), with the response and progression statuses both determined by the blinded, central independent review. The analysis will be descriptive for each treatment group only.

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Duration of Response (DOR)	11.1 Months Interval 9.2 to 18.3	9.3 Months Interval 7.7 to 11.0

SECONDARY outcome

Timeframe: From 04 Feb 2014 till 19 June 2018

Population: Intent to Treat

An analysis of TEAEs with an onset within the first 24 weeks of treatment was performed to examine and compare the incidence of events across an equal period for each treatment arm.Twenty-four weeks was anticipated to be the median exposure to ofatumumab.

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=159 Participants Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Treatment-Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values	150 Participants	143 Participants

SECONDARY outcome

Timeframe: Cycle 2, Cycle 3, and Cycle 7

Population: Intent to Treat for duvelisib patients, no PK samples were collected for ofatumumab patients.

Number of subjects with samples available for duvelisib Pharmacokinetics (PK)

Outcome measures

Outcome measures
Measure	Duvelisib n=160 Participants Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Number of Subjects With Samples Available for Duvelisib Pharmacokinetics (PK)	158 participants	—

Adverse Events

Duvelisib

Serious events: 124 serious events

Other events: 149 other events

Deaths: 78 deaths

Ofatumumab

Serious events: 50 serious events

Other events: 130 other events

Deaths: 70 deaths

Serious adverse events

Other adverse events

Additional Information

Beth Gregory, PharmD, MBA

Secura Bio, Inc.

Phone: 1-702-254-0011

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Duvelisib n=158 participants at risk Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Ofatumumab n=155 participants at risk Ofatumumab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.
Blood and lymphatic system disorders Neutropenia	33.5% 53/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	20.6% 32/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Blood and lymphatic system disorders Anaemia	24.7% 39/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	10.3% 16/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Blood and lymphatic system disorders Thrombocytopenia	17.1% 27/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.8% 9/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Diarrhoea	50.0% 79/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	12.3% 19/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Nausea	24.1% 38/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	11.0% 17/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Constipation	17.1% 27/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	7.7% 12/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Vomiting	14.6% 23/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	6.5% 10/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Abdominal pain	10.8% 17/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Dyspepsia	5.7% 9/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	2.6% 4/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Abdominal pain upper	5.7% 9/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	3.2% 5/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Paraesthesia oral	0.00% 0/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	6.5% 10/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Colitis	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	0.65% 1/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Gastrointestinal disorders Dry mouth	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	0.65% 1/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
General disorders Pyrexia	29.1% 46/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	9.7% 15/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
General disorders Fatigue	15.8% 25/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	11.6% 18/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
General disorders Asthenia	12.7% 20/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	11.0% 17/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
General disorders Oedema peripheral	10.1% 16/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	4.5% 7/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Infections and infestations Pneumonia	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	2.6% 4/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Infections and infestations Bronchitis	12.7% 20/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	7.7% 12/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Infections and infestations Upper respiratory tract infection	13.9% 22/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	7.7% 12/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Infections and infestations Nasopharyngitis	8.2% 13/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	2.6% 4/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Infections and infestations Respiratory tract infection	7.0% 11/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Injury, poisoning and procedural complications Infusion related reaction	1.3% 2/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	18.1% 28/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Investigations Alanine aminotransferase increased	8.2% 13/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Investigations Weight decreased	13.3% 21/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Investigations Aspartate aminotransferase increased	9.5% 15/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Metabolism and nutrition disorders Dehydration	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	0.65% 1/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Metabolism and nutrition disorders Hypokalaemia	10.1% 16/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Metabolism and nutrition disorders Hyperkalaemia	7.0% 11/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	3.2% 5/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Metabolism and nutrition disorders Decreased appetite	15.2% 24/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	3.2% 5/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 9/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 11/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	3.2% 5/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Musculoskeletal and connective tissue disorders Back pain	7.6% 12/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.2% 8/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Musculoskeletal and connective tissue disorders Muscle spasms	4.4% 7/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.2% 8/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Nervous system disorders Dizziness	8.2% 13/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	3.2% 5/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Nervous system disorders Headache	8.2% 13/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	8.4% 13/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Nervous system disorders Paraesthesia	4.4% 7/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	9.7% 15/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Psychiatric disorders Insomnia	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.8% 9/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.7% 9/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.9% 3/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Respiratory, thoracic and mediastinal disorders Productive cough	5.1% 8/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.3% 2/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Respiratory, thoracic and mediastinal disorders Cough	22.8% 36/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	14.2% 22/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.9% 14/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.8% 9/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Skin and subcutaneous tissue disorders Rash	10.8% 17/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	11.6% 18/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.7% 9/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	1.3% 2/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Skin and subcutaneous tissue disorders Pruritus	7.0% 11/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.8% 9/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Vascular disorders Hypertension	8.2% 13/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	2.6% 4/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.
Vascular disorders Hypotension	2.5% 4/158 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.	5.2% 8/155 • 39 months Safety data rerun to include treatment-emergent adverse events that occurred on Day 1.