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

• Sponsor: SecuraBio (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02004522
• Collaborator: (none)
• Enrollment: 319
• Locations: 92
• Arms: 2
• Duration (Months): 91
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

A Phase 3 clinical trial to examine the efficacy of duvelisib monotherapy versus ofatumumab monotherapy in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Drug: Duvelisib; Drug: Ofatumumab	Phase 3

Detailed Description

This is an open-label, two- arm, randomized phase 3, superiority trial designed to evaluate the efficacy and safety of duvelisib compared to ofatumumab administered to patients who have been diagnosed with CLL/SLL whose disease is relapsed or refractory.

Approximately 150 subjects will receive a starting dose of 25 mg duvelisib BID initially over the course of 21-day treatment cycle followed by 28-day treatment cycles for up to 18 cycles or until disease progression or unacceptable toxicity (whichever comes first). After 18 complete cycles of treatment, subjects may receive additional cycles of duvelisib until disease progression or unacceptable toxicity if they, in the judgment of the Investigator, may derive benefit from continued treatment, and if the subject meets the criteria for additional treatment at Cycle 19 Day 1.

Approximately 150 subjects will receive a starting dose of 300 mg ofatumumab on Day 1 followed by seven weekly doses of 2000 mg. Thereafter, subjects will receive 2000 mg ofatumumab once every month for four months. Administration of ofatumumab will not exceed the 12 doses (within 7 cycles).

Study Design

• Study Type: Interventional
• Actual Enrollment: 319 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (DUO)
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: May 19, 2017
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duvelisib Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Drug: Duvelisib; PI3K Inhibitor; Other Names: Copiktra, IPI-145, PI3K Inhibitor
Active Comparator: Ofatumumab Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL	Drug: Ofatumumab; monoclonal antibody; Other Names: Arzerra

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [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]

   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.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Until disease progression or unacceptable toxicity assessed up to 6 years]

   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.

2. Number of Subjects With Hematologic Improvements [3 years]

   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.

3. Overall Survival [Every 6 months for up to 3 years after first dose]

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

4. Lymph Node Response Rate [3 years]

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

5. Duration of Response (DOR) [Time from the first documentation of response to first documentation of progressive disease or death due to any cause]

   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.

6. Treatment- Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values [04 Feb 2014 - 19 June 2018]

   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.

7. Number of Subjects With Samples Available for Duvelisib Pharmacokinetics (PK) [Cycle 2, Cycle 3, and Cycle 7]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ≥ B and/or Rai Stage ≥ I)

• Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy

• Not appropriate for treatment with a purine-based analogue regimen (per National Comprehensive Cancer Network [NCCN] or European Society for Medical Oncology [ESMO] guidelines), including relapse ≤ 36 months from a purine-based chemoimmunotherapy regimen or relapse ≤ 24 months from a purine-based monotherapy regimen

• A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification

• Measurable disease with a lymph node or tumor mass > 1.5 cm in at least one dimension as assessed by computed tomography (CT)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] ≥ 60%)

• Willingness by subject to be randomized to receive either ofatumumab or duvelisib at the dose and schedule defined in the protocol

• Must meet the following laboratory parameters:

1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN)

2. Total bilirubin ≤ 1.5 x ULN

3. Serum creatinine ≤ 2.0 x ULN

4. Hemoglobin ≥ 8.0 g/dL with or without transfusion support

5. Platelet count ≥ 10,000 μL with or without transfusion support

• For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women ≤ 55 years] or 12 consecutive months [women > 55 years])

• Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception

• Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements

• Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed

Exclusion Criteria:

• History of Richter's transformation or prolymphocytic leukemia

• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requiring > 20 mg once daily (QD) of prednisone (or equivalent) to maintain hemoglobin > 8.0 g/dL or platelets > 10,000 μL without transfusion support

• Refractory to ofatumumab (progression or relapse <12 months of receiving ofatumumab therapy or <24 months of receiving an ofatumumab- containing regimen)

• Prior allogeneic transplant (prior autologous stem cell transplant >6 months prior to study entry is permitted)

• Known central nervous system lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization

• Use of any of the following medications or procedures within the specified timeframe:

• Use of live or live attenuated vaccines within 30 days prior to randomization

• Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization

• Tyrosine kinase inhibitor within 7 days of randomization

• Other investigational therapy (not included above) within 3 weeks of randomization

• Previous treatment with a PI3K inhibitor or BTK inhibitor

• Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD

• History of tuberculosis treatment within the preceding two years

• Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring IV antimicrobial, antifungal or antiviral agents)

• Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at randomization

• Human immunodeficiency virus (HIV) infection

• Prior, current, or chronic hepatitis B or hepatitis C infection

• History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)

• Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)

• Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) Note: This criterion does not apply to subjects with a right or left bundle branch block (BBB)

• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk while participating in this study

• Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease free for ≥2 years

• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months

• Administration of medications or foods that are strong inhibitors or inducers of CYP3A within 2 weeks of randomization

• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)

• Major surgery or invasive intervention within 4 weeks prior to randomization

• Pregnant or breastfeeding women

• Hypersensitivity to ofatumumab or its excipients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Jolla	California	United States	92093-0698
2		Denver	Colorado	United States	80218
3		Altamonte Springs	Florida	United States	32701
4		Bonita Springs	Florida	United States	34135-4529
5		Bradenton	Florida	United States	34209
6		Brandon	Florida	United States	33511
7		Cape Coral	Florida	United States	33990
8		Clearwater	Florida	United States	33761
9		Englewood	Florida	United States	34223
10		Fort Myers	Florida	United States	33916
11		Gainesville	Florida	United States	32605
12		Hudson	Florida	United States	34667
13		Inverness	Florida	United States	34453
14		Largo	Florida	United States	33777
15		Naples	Florida	United States	34119
16		New Port Richey	Florida	United States	34655
17		Orange City	Florida	United States	32763
18		Orlando	Florida	United States	32806
19		Port Charlotte	Florida	United States	33980
20		Saint Petersburg	Florida	United States	33705
21		Sarasota	Florida	United States	34236
22		Spring Hill	Florida	United States	34608
23		Tampa	Florida	United States	33607
24		Tavares	Florida	United States	32778
25		Venice	Florida	United States	34292
26		Crestview Hills	Kentucky	United States	41017
27		Boston	Massachusetts	United States	02114
28		Boston	Massachusetts	United States	02115
29		Saint Louis	Missouri	United States	63130
30		Hackensack	New Jersey	United States	07601
31		New Brunswick	New Jersey	United States	08903
32		New York	New York	United States	10032
33		New York	New York	United States	10065
34		Cincinnati	Ohio	United States	45236
35		Fairfield	Ohio	United States	45014
36		Nashville	Tennessee	United States	37203
37		Charlottesville	Virginia	United States	22903
38		Bedford Park		Australia	5042
39		East Melbourne		Australia	3002
40		Melbourne		Australia	3058
41		Vienna		Austria	1090
42		Wels		Austria	4600
43		Wien		Austria	1130
44		Bruxelles		Belgium	1000
45		Bruxelles		Belgium	1200
46		Gent		Belgium	9000
47		Leuven		Belgium	3000
48		Sint- Niklaas		Belgium	9100
49		Argenteuil		France	95107
50		Bobigny		France	93009
51		Bordeaux		France	33076
52		Caen		France	14033
53		Clermont-Ferrand		France	63100
54		La Roche Sur Yon		France	85025
55		Limoges Cedex		France	87042
56		Nantes		France	44000
57		Rennes		France	35033
58		Vendœuvres		France	54511
59		Berlin		Germany	10707
60		Köln		Germany	50937
61		Leer		Germany	26789
62		Rostock		Germany	18057
63		Ulm		Germany	89081
64		Budapest		Hungary	1083
65		Budapest		Hungary	1122
66		Debrecen		Hungary	4032
67		Gyor		Hungary	9024
68		Kaposvár		Hungary	7400
69		Pecs		Hungary	7624
70		Szeged		Hungary	6725
71		Catania		Italy	95124
72		Lecce		Italy	73100
73		Meldola		Italy	47014
74		Milano		Italy	20132
75		Milano		Italy	20162
76		Padova		Italy	35128
77		Ravenna		Italy	48121
78		Rimini		Italy	47923
79		Roma		Italy	00133
80		Auckland		New Zealand	1023
81		Palmerston North		New Zealand	4442
82		Barcelona		Spain	08035
83		Barcelona		Spain	08036
84		Barcelona		Spain	08041
85		Madrid		Spain	28033
86		Madrid		Spain	28050
87		Pamplona		Spain	31008
88		Bournemouth		United Kingdom	BH7 7DW
89		Leeds		United Kingdom	LS9 7TF
90		Manchester		United Kingdom	M20 4BX
91		Nottingham		United Kingdom	NG5 1PB
92		Oxford		United Kingdom	OX3 7JL

Sponsors and Collaborators

• SecuraBio

Investigators

• Study Director: David Cohan, MD, SecuraBio Chief Medical Officer

Study Documents (Full-Text)

• Study Protocol - Feb 9, 2017
• Statistical Analysis Plan - May 9, 2017

More Information

Publications

None provided.

• Responsible Party: SecuraBio
• ClinicalTrials.gov Identifier: NCT02004522
• Other Study ID Numbers: IPI-145-07
• First Posted: Dec 9, 2013
• Last Update Posted: Jan 5, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by SecuraBio: Phase 3; CLL/SLL; Pi3K
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	Duvelisib	Ofatumumab	Total
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL	Total of all reporting groups
Overall Participants	160	159	319
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	48 30%	54 34%	102 32%
>=65 years	112 70%	105 66%	217 68%
Sex: Female, Male (Count of Participants)
Female	64 40%	64 40.3%	128 40.1%
Male	96 60%	95 59.7%	191 59.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 5%	7 4.4%	15 4.7%
Not Hispanic or Latino	130 81.3%	133 83.6%	263 82.4%
Unknown or Not Reported	22 13.8%	19 11.9%	41 12.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.6%	1 0.6%	2 0.6%
White	150 93.8%	142 89.3%	292 91.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	9 5.6%	16 10.1%	25 7.8%
Region of Enrollment (participants) [Number]
New Zealand	6 3.8%	6 3.8%	12 3.8%
Austria	3 1.9%	8 5%	11 3.4%
Belgium	13 8.1%	14 8.8%	27 8.5%
Hungary	35 21.9%	30 18.9%	65 20.4%
United States	30 18.8%	21 13.2%	51 16%
Italy	23 14.4%	18 11.3%	41 12.9%
United Kingdom	7 4.4%	10 6.3%	17 5.3%
Australia	9 5.6%	12 7.5%	21 6.6%
France	12 7.5%	18 11.3%	30 9.4%
Germany	1 0.6%	3 1.9%	4 1.3%
Spain	21 13.1%	19 11.9%	40 12.5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Median (95% Confidence Interval) [Months]	13.3	9.9

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	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.
Time Frame	Until disease progression or unacceptable toxicity assessed up to 6 years

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Count of Participants [Participants]	118 73.8%	72 45.3%

3. Secondary Outcome

Title	Number of Subjects With Hematologic Improvements
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Subjects With Abnormal Hematologic Values at Baseline

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	94	95
Count of Participants [Participants]	56 35%	51 32.1%

4. Secondary Outcome

Title	Overall Survival
Description	A stratified Cox regression analysis was used to test for any treatment effect.
Time Frame	Every 6 months for up to 3 years after first dose

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Median (95% Confidence Interval) [Months]	NA	NA

5. Secondary Outcome

Title	Lymph Node Response Rate
Description	Lymph node response defined as greater than or equal to 50% decrease in the SPD of target lymph nodes
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Count of Participants [Participants]	136 85%	25 15.7%

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	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.
Time Frame	Time from the first documentation of response to first documentation of progressive disease or death due to any cause

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Median (95% Confidence Interval) [Months]	11.1	9.3

7. Secondary Outcome

Title	Treatment- Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values
Description	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.
Time Frame	04 Feb 2014 - 19 June 2018

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Duvelisib	Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules	Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
Measure Participants	160	159
Count of Participants [Participants]	150 93.8%	143 89.9%

8. Secondary Outcome

Title	Number of Subjects With Samples Available for Duvelisib Pharmacokinetics (PK)
Description	Number of subjects with samples available for duvelisib Pharmacokinetics (PK)
Time Frame	Cycle 2, Cycle 3, and Cycle 7

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules
Measure Participants	160
Number [participants]	158 98.8%

Adverse Events

Time Frame	39 months
Arm/Group Title	Duvelisib		Ofatumumab
Arm/Group Description	Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules		Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL Ofatumumab
All Cause Mortality
	Duvelisib		Ofatumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/158 (12%)		7/155 (4.5%)
Serious Adverse Events
	Duvelisib		Ofatumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/158 (72.8%)		50/155 (32.3%)
Blood and lymphatic system disorders
Febrile neutropenia	10/158 (6.3%)		3/155 (1.9%)
Anaemia	2/158 (1.3%)		2/155 (1.3%)
Haemolytic anaemia	2/158 (1.3%)		1/155 (0.6%)
Pancytopenia	2/158 (1.3%)		0/155 (0%)
Neutropenia	1/158 (0.6%)		0/155 (0%)
Thrombocytopenia	1/158 (0.6%)		0/155 (0%)
Lymph node pain	0/158 (0%)		1/155 (0.6%)
Cardiac disorders
Atrial fibrillation	2/158 (1.3%)		1/155 (0.6%)
Cardiac failure	2/158 (1.3%)		1/155 (0.6%)
Cardiac failure congestive	1/158 (0.6%)		0/155 (0%)
Myocardial infarction	1/158 (0.6%)		0/155 (0%)
Pericarditis	1/158 (0.6%)		0/155 (0%)
Ventricular tachycardia	1/158 (0.6%)		0/155 (0%)
Angina pectoris	0/158 (0%)		1/155 (0.6%)
Tachycardia	0/158 (0%)		1/155 (0.6%)
Gastrointestinal disorders
Colitis	19/158 (12%)		1/155 (0.6%)
Diarrhoea	16/158 (10.1%)		1/155 (0.6%)
Enterocolitis	2/158 (1.3%)		1/155 (0.6%)
Gastritis	2/158 (1.3%)		0/155 (0%)
Upper gastrointestinal haemorrhage	2/158 (1.3%)		0/155 (0%)
Abdominal pain	1/158 (0.6%)		1/155 (0.6%)
Colitis ischaemic	1/158 (0.6%)		0/155 (0%)
Enteritis	1/158 (0.6%)		0/155 (0%)
Mallory-Weiss syndrome	1/158 (0.6%)		0/155 (0%)
Pancreatitis acute	1/158 (0.6%)		0/155 (0%)
Proctitis	1/158 (0.6%)		0/155 (0%)
Oesophageal ulcer	0/158 (0%)		1/155 (0.6%)
Portal hypertensive gastropathy	0/158 (0%)		1/155 (0.6%)
General disorders
Pyrexia	7/158 (4.4%)		1/155 (0.6%)
General physical health deterioration	4/158 (2.5%)		0/155 (0%)
Death	1/158 (0.6%)		0/155 (0%)
Mucosal inflammation	1/158 (0.6%)		0/155 (0%)
Multi-organ failure	1/158 (0.6%)		0/155 (0%)
Oedema peripheral	1/158 (0.6%)		0/155 (0%)
Sudden death	1/158 (0.6%)		0/155 (0%)
Disease progression	0/158 (0%)		2/155 (1.3%)
Fatigue	0/158 (0%)		1/155 (0.6%)
Infusion site extravasation	0/158 (0%)		1/155 (0.6%)
Hepatobiliary disorders
Cholecystitis	0/158 (0%)		1/155 (0.6%)
Hepatic failure	0/158 (0%)		1/155 (0.6%)
Immune system disorders
Contrast media allergy	0/158 (0%)		1/155 (0.6%)
Drug hypersensitivity	0/158 (0%)		1/155 (0.6%)
Infections and infestations
Pneumonia	23/158 (14.6%)		5/155 (3.2%)
Bronchitis	5/158 (3.2%)		1/155 (0.6%)
Gastroenteritis	4/158 (2.5%)		1/155 (0.6%)
Bronchopulmonary aspergillosis	3/158 (1.9%)		0/155 (0%)
Pneumocystis jirovecii pneumonia	3/158 (1.9%)		0/155 (0%)
Pneumonia pseudomonas aeruginosa	3/158 (1.9%)		0/155 (0%)
Sepsis	3/158 (1.9%)		1/155 (0.6%)
Upper respiratory tract infection	3/158 (1.9%)		0/155 (0%)
Clostridium difficile colitis	2/158 (1.3%)		0/155 (0%)
Influenza	2/158 (1.3%)		0/155 (0%)
Lower respiratory tract infection	2/158 (1.3%)		1/155 (0.6%)
Pneumonia bacterial	2/158 (1.3%)		2/155 (1.3%)
Pneumonia pneumococcal	2/158 (1.3%)		0/155 (0%)
Pneumonia staphylococcal	2/158 (1.3%)		0/155 (0%)
Pseudomonal sepsis	2/158 (1.3%)		0/155 (0%)
Skin infection	2/158 (1.3%)		0/155 (0%)
Aspergillus infection	1/158 (0.6%)		0/155 (0%)
Bronchiolitis	1/158 (0.6%)		0/155 (0%)
Bronchitis viral	1/158 (0.6%)		0/155 (0%)
Bronchopneumonia	1/158 (0.6%)		0/155 (0%)
Campylobacter gastroenteritis	1/158 (0.6%)		0/155 (0%)
Cytomegalovirus colitis	1/158 (0.6%)		0/155 (0%)
Diverticulitis	1/158 (0.6%)		0/155 (0%)
Enterococcal infection	1/158 (0.6%)		0/155 (0%)
Enterococcal sepsis	1/158 (0.6%)		0/155 (0%)
Escherichia sepsis	1/158 (0.6%)		2/155 (1.3%)
Escherichia urinary tract infection	1/158 (0.6%)		2/155 (1.3%)
Fungal infection	1/158 (0.6%)		0/155 (0%)
Fungal oesophagitis	1/158 (0.6%)		0/155 (0%)
Gastroenteritis viral	1/158 (0.6%)		0/155 (0%)
Haemophilus infection	1/158 (0.6%)		0/155 (0%)
Infusion site cellulitis	1/158 (0.6%)		0/155 (0%)
Lobar pneumonia	1/158 (0.6%)		0/155 (0%)
Lower respiratory tract infection viral	1/158 (0.6%)		0/155 (0%)
Lung infection	1/158 (0.6%)		0/155 (0%)
Pneumonia escherichia	1/158 (0.6%)		0/155 (0%)
Pneumonia klebsiella	1/158 (0.6%)		0/155 (0%)
Pneumonia mycoplasmal	1/158 (0.6%)		0/155 (0%)
Pneumonia respiratory syncytial viral	1/158 (0.6%)		0/155 (0%)
Pseudomonas bronchitis	1/158 (0.6%)		0/155 (0%)
Pyelonephritis	1/158 (0.6%)		0/155 (0%)
Respiratory tract infection bacterial	1/158 (0.6%)		0/155 (0%)
Septic shock	1/158 (0.6%)		0/155 (0%)
Streptococcal bacteraemia	1/158 (0.6%)		1/155 (0.6%)
Streptococcal sepsis	1/158 (0.6%)		0/155 (0%)
Urinary tract infection	1/158 (0.6%)		0/155 (0%)
Wound infection staphylococcal	1/158 (0.6%)		0/155 (0%)
Chronic sinusitis	0/158 (0%)		1/155 (0.6%)
Clostridium difficile infection	0/158 (0%)		1/155 (0.6%)
Device related infection	0/158 (0%)		1/155 (0.6%)
Herpes virus infection	0/158 (0%)		1/155 (0.6%)
Neutropenic sepsis	0/158 (0%)		1/155 (0.6%)
Pneumonia viral	0/158 (0%)		1/155 (0.6%)
Injury, poisoning and procedural complications
Accidental overdose	1/158 (0.6%)		0/155 (0%)
Cervical vertebral fracture	1/158 (0.6%)		0/155 (0%)
Femur fracture	1/158 (0.6%)		0/155 (0%)
Splenic rupture	1/158 (0.6%)		0/155 (0%)
Subdural haematoma	1/158 (0.6%)		0/155 (0%)
Traumatic haematoma	1/158 (0.6%)		0/155 (0%)
Fall	0/158 (0%)		1/155 (0.6%)
Infusion related reaction	0/158 (0%)		3/155 (1.9%)
Investigations
Alanine aminotransferase increased	1/158 (0.6%)		0/155 (0%)
Aspartate aminotransferase increased	1/158 (0.6%)		0/155 (0%)
Lipase increased	1/158 (0.6%)		0/155 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/158 (0.6%)		0/155 (0%)
Hyponatraemia	1/158 (0.6%)		1/155 (0.6%)
Malnutrition	1/158 (0.6%)		0/155 (0%)
Tumour lysis syndrome	1/158 (0.6%)		0/155 (0%)
Hypercalcaemia	0/158 (0%)		2/155 (1.3%)
Hyperglycaemia	0/158 (0%)		1/155 (0.6%)
Hyperkalaemia	0/158 (0%)		1/155 (0.6%)
Hypervolaemia	0/158 (0%)		2/155 (1.3%)
Musculoskeletal and connective tissue disorders
Arthritis	1/158 (0.6%)		0/155 (0%)
Bone pain	1/158 (0.6%)		0/155 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intestinal adenocarcinoma	1/158 (0.6%)		0/155 (0%)
Malignant melanoma	1/158 (0.6%)		1/155 (0.6%)
Neuroendocrine carcinoma of the skin	1/158 (0.6%)		0/155 (0%)
Glioblastoma multiforme	0/158 (0%)		1/155 (0.6%)
Malignant pleural effusion	0/158 (0%)		1/155 (0.6%)
Squamous cell carcinoma	0/158 (0%)		1/155 (0.6%)
Squamous cell carcinoma of lung	0/158 (0%)		1/155 (0.6%)
Nervous system disorders
Haemorrhagic stroke	2/158 (1.3%)		0/155 (0%)
Brain stem haemorrhage	1/158 (0.6%)		0/155 (0%)
Dementia	1/158 (0.6%)		0/155 (0%)
Mental impairment	1/158 (0.6%)		0/155 (0%)
Dizziness	0/158 (0%)		1/155 (0.6%)
Headache	0/158 (0%)		1/155 (0.6%)
Ischaemic stroke	0/158 (0%)		1/155 (0.6%)
Renal and urinary disorders
Renal failure acute	4/158 (2.5%)		2/155 (1.3%)
Nephrolithiasis	1/158 (0.6%)		0/155 (0%)
Renal colic	1/158 (0.6%)		0/155 (0%)
Renal failure	1/158 (0.6%)		0/155 (0%)
Renal failure chronic	1/158 (0.6%)		0/155 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	6/158 (3.8%)		0/155 (0%)
Pulmonary embolism	3/158 (1.9%)		2/155 (1.3%)
Dyspnoea	2/158 (1.3%)		0/155 (0%)
Interstitial lung disease	2/158 (1.3%)		0/155 (0%)
Acute respiratory distress syndrome	1/158 (0.6%)		0/155 (0%)
Chronic obstructive pulmonary disease	1/158 (0.6%)		0/155 (0%)
Lung disorder	1/158 (0.6%)		0/155 (0%)
Pleural effusion	1/158 (0.6%)		0/155 (0%)
Pleural haemorrhage	1/158 (0.6%)		0/155 (0%)
Pneumonia aspiration	1/158 (0.6%)		0/155 (0%)
Respiratory failure	1/158 (0.6%)		0/155 (0%)
Laryngeal stenosis	0/158 (0%)		1/155 (0.6%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	4/158 (2.5%)		0/155 (0%)
Dermatitis exfoliative	2/158 (1.3%)		0/155 (0%)
Rash	2/158 (1.3%)		0/155 (0%)
Dermatitis allergic	1/158 (0.6%)		0/155 (0%)
Rash erythematous	1/158 (0.6%)		0/155 (0%)
Rash maculo-papular	1/158 (0.6%)		0/155 (0%)
Vascular disorders
Deep vein thrombosis	2/158 (1.3%)		1/155 (0.6%)
Hypertension	1/158 (0.6%)		0/155 (0%)
Thrombosis	1/158 (0.6%)		0/155 (0%)
Peripheral embolism	0/158 (0%)		1/155 (0.6%)
Other (Not Including Serious) Adverse Events
	Duvelisib		Ofatumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	154/158 (97.5%)		139/155 (89.7%)
Blood and lymphatic system disorders
Neutropenia	52/158 (32.9%)		32/155 (20.6%)
Anaemia	35/158 (22.2%)		16/155 (10.3%)
Thrombocytopenia	22/158 (13.9%)		9/155 (5.8%)
Gastrointestinal disorders
Diarrhoea	75/158 (47.5%)		19/155 (12.3%)
Nausea	37/158 (23.4%)		17/155 (11%)
Constipation	26/158 (16.5%)		13/155 (8.4%)
Vomiting	23/158 (14.6%)		10/155 (6.5%)
Abdominal pain	15/158 (9.5%)		3/155 (1.9%)
Dyspepsia	9/158 (5.7%)		4/155 (2.6%)
Abdominal pain upper	8/158 (5.1%)		5/155 (3.2%)
Paraesthesia oral	0/158 (0%)		10/155 (6.5%)
General disorders
Pyrexia	44/158 (27.8%)		15/155 (9.7%)
Fatigue	20/158 (12.7%)		18/155 (11.6%)
Asthenia	18/158 (11.4%)		17/155 (11%)
Oedema peripheral	15/158 (9.5%)		7/155 (4.5%)
Infections and infestations
Upper respiratory tract infection	22/158 (13.9%)		12/155 (7.7%)
Bronchitis	17/158 (10.8%)		12/155 (7.7%)
Nasopharyngitis	12/158 (7.6%)		4/155 (2.6%)
Respiratory tract infection	11/158 (7%)		3/155 (1.9%)
Pneumonia	9/158 (5.7%)		4/155 (2.6%)
Injury, poisoning and procedural complications
Infusion related reaction	2/158 (1.3%)		28/155 (18.1%)
Investigations
Weight decreased	18/158 (11.4%)		3/155 (1.9%)
Aspartate aminotransferase increased	14/158 (8.9%)		3/155 (1.9%)
Alanine aminotransferase increased	12/158 (7.6%)		3/155 (1.9%)
Metabolism and nutrition disorders
Decreased appetite	20/158 (12.7%)		5/155 (3.2%)
Hypokalaemia	15/158 (9.5%)		3/155 (1.9%)
Hyperkalaemia	11/158 (7%)		5/155 (3.2%)
Dehydration	8/158 (5.1%)		1/155 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	10/158 (6.3%)		8/155 (5.2%)
Pain in extremity	9/158 (5.7%)		3/155 (1.9%)
Arthralgia	8/158 (5.1%)		5/155 (3.2%)
Muscle spasms	7/158 (4.4%)		8/155 (5.2%)
Nervous system disorders
Headache	13/158 (8.2%)		13/155 (8.4%)
Dizziness	11/158 (7%)		5/155 (3.2%)
Paraesthesia	7/158 (4.4%)		15/155 (9.7%)
Psychiatric disorders
Insomnia	7/158 (4.4%)		9/155 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	33/158 (20.9%)		22/155 (14.2%)
Dyspnoea	14/158 (8.9%)		9/155 (5.8%)
Rhinorrhoea	9/158 (5.7%)		3/155 (1.9%)
Skin and subcutaneous tissue disorders
Rash	15/158 (9.5%)		18/155 (11.6%)
Pruritus	11/158 (7%)		9/155 (5.8%)
Vascular disorders
Hypertension	12/158 (7.6%)		4/155 (2.6%)
Hypotension	4/158 (2.5%)		8/155 (5.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.