A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma (DYNAMO)

• Sponsor: SecuraBio (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01882803
• Collaborator: (none)
• Enrollment: 129
• Locations: 69
• Arm: 1
• Anticipated Duration (Months): 101.7
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Phase 2 clinical trial to evaluate the safety and efficacy of duvelisib as a monotherapy in subjects with iNHL (Follicular Lymphoma, Marginal Zone Lymphoma, or Small Lymphocytic Lymphoma) that is refractory to rituximab and to either chemotherapy or RIT.

Condition or Disease	Intervention/Treatment	Phase
Indolent Non-Hodgkin Lymphoma	Drug: Duvelisib	Phase 2

Detailed Description

This is an open-label, single arm safety and efficacy study of duvelisib administered orally to subjects who have been diagnosed with iNHL (Follicular Lymphoma, Marginal Zone Lymphoma, or Small Lymphocytic Lymphoma) whose disease is refractory to rituximab and to either chemotherapy or RIT.

Approximately 120 subjects will receive 25 mg duvelisib BID over the course of 28-day treatment cycles for up to 13 cycles.

After completing 13 treatment cycles of duvelisib, subjects may continue to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 13 cycles, subjects must have evidence of response (CR or PR) according to the IWG criteria1 by the end of Cycle 13.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma (DYNAMO)
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: May 1, 2016
• Anticipated Study Completion Date: Oct 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duvelisib	Drug: Duvelisib; PI3K Inhibitor; Other Names: Copiktra, IPI-145

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) in All Subjects During Treatment With Duvelisib Based on Standard Response. [Every 8-16 weeks while on treatment with duvelisib; an expected average on-treatment duration of response follow-up of 24 months]

   Summary of Best Overall Response and Overall Response Rate per IRC Assessment (FAS)

Secondary Outcome Measures

1. Number of Subjects With Treatment- Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values [Every 2-8 weeks; up to 30 days after the last dose of duvelisib.]

   Treatment-Emergent Adverse Events Occurring in ≥ 10% Subjects, by SOC and PT (FAS)

2. Duration of Response [Every 8-16 weeks; for an average duration of response follow-up of 24 months]

   Duration of Response per IRC Full Analysis Set

3. Progression-free Survival [Every 8-16 weeks; for an average response / progression follow-up of 24 months]

   Progression Free Survival per IRC Full Analysis Set

4. Overall Survival [Every 16 weeks; for an average survival follow-up of 24 months]

   Overall Survival Full Analysis Set

5. PK Plasma Concentrations of Duvelisib and Its Metabolite(s) [Every 4 weeks for 12 weeks]

   Pharmacokinetics - duvelisib concentration (ng/mL) Full Analysis Set

6. Time to Response (TTR) [First dose to first documentation of complete or partial response]

   Time to Response per IRC Full Analysis Set

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects who have been diagnosed with indolent NHL that has progressed.

• Subjects must have exhibited lack of CR or PR or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT.

• Subjects must have rituximab-refractory disease, defined as lack of CR or PR or PD within 6 months of last dose.

• Measurable disease with a lymph node or tumor mass ≥1.5 cm in at least one dimension by CT, PET/CT or MRI.

• Adequate renal and hepatic function.

Exclusion Criteria:

• Candidate for potentially curative therapies in the opinion of the investigator.

• Previous treatment with a PI3K inhibitor or BTK inhibitor.

• Prior history of allogeneic hematopoietic stem cell transplant (HSCT).

• Prior chemotherapy, cancer immunosuppressive therapy, or other investigational agents within 4 weeks before first dose of study drug.

• Grade 3B FL and/or clinical evidence of transformation to a more aggressive subtype of lymphoma.

• Symptomatic central nervous system (CNS) NHL.

• Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment.

• Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis C virus antibodies (HCV Ab) or hepatitis B surface antigen (HBsAg) or hepatitis B core antibodies (HBcAb)

• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to first dose of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90095-6984
2		Whittier	California	United States	90603
3		Denver	Colorado	United States	80218
4		Fort Myers	Florida	United States	39916
5		Saint Petersburg	Florida	United States	33705
6		Tallahassee	Florida	United States	32308
7		Atlanta	Georgia	United States	30322
8		Chicago	Illinois	United States	60637
9		Louisville	Kentucky	United States	40207
10		Baltimore	Maryland	United States	21204
11		Baltimore	Maryland	United States	21229
12		Boston	Massachusetts	United States	02215
13		Saint Louis	Missouri	United States	63110
14		Howell	New Jersey	United States	07731
15		Morristown	New Jersey	United States	07962
16		New York	New York	United States	10021
17		Rockville Centre	New York	United States	11510
18		Canton	Ohio	United States	44718
19		Lawton	Oklahoma	United States	73505
20		Oklahoma City	Oklahoma	United States	73104
21		Philadelphia	Pennsylvania	United States	01911
22		Nashville	Tennessee	United States	37203
23		Dallas	Texas	United States	75246
24		Lynchburg	Virginia	United States	24501
25		Lesnoy	Minsk Region	Belarus	223040
26		Brest		Belarus	224027
27		Minsk		Belarus	220013
28		Vitebsk		Belarus	210603
29		Gent		Belgium	9000
30		Kortrijk		Belgium	8500
31		Sofia		Bulgaria	1233
32		Sofia		Bulgaria	1407
33		Sofia		Bulgaria	1431
34		Sofia		Bulgaria	1756
35		Toronto	Ontario	Canada	M5G 2M9
36		Gatineau	Quebec	Canada	J8P7H2
37		Montreal	Quebec	Canada	H3T 1E2
38		Brno		Czechia	625-00
39		Ostrava-Poruba		Czechia	708-52
40		Angers Cedex 09		France	49933
41		Bordeaux		France	33076
42		Clermont-Ferrand		France	63000
43		Marseille		France	13005
44		Pierre Benite		France	69495
45		Tbilisi		Georgia	0186
46		Budapest		Hungary	1083
47		Budapest		Hungary	1122
48		Debrecen		Hungary	4032
49		Bologna		Italy	40138
50		Brescia		Italy	25123
51		Busto Arsizio		Italy	21052
52		Genova		Italy	16132
53		Meldola		Italy	47014
54		Milano		Italy	20162
55		Modena		Italy	41124
56		Orbassano		Italy	10043
57		Parma		Italy	43100
58		Ravenna		Italy	48121
59		Rimini		Italy	47923
60		Varese		Italy	21100
61		Barcelona		Spain	08036
62		Madrid		Spain	28222
63		Salamanca		Spain	37007
64		Cardiff		United Kingdom	CF 14 4XW
65		Chelsea		United Kingdom
66		Liverpool		United Kingdom	L7 8XP
67		London		United Kingdom	NW1 2PG
68		London		United Kingdom	W1G 6AD
69		Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• SecuraBio

Investigators

• Study Chair: Hagop Youssoufian, MD, Verastem, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SecuraBio
• ClinicalTrials.gov Identifier: NCT01882803
• Other Study ID Numbers: IPI-145-06
• First Posted: Jun 20, 2013
• Last Update Posted: Mar 17, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by SecuraBio: PI3K Inhibitor
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin

Study Results

Participant Flow

Recruitment Details	This multicenter, multinational study enrolled subjects at 56 medical clinics across 12 countries.

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	129
COMPLETED	35
NOT COMPLETED	94

Baseline Characteristics

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Overall Participants	129
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	64 49.6%
>=65 years	65 50.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.6 (11.69)
Sex: Female, Male (Count of Participants)
Female	41 31.8%
Male	88 68.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 2.3%
Not Hispanic or Latino	118 91.5%
Unknown or Not Reported	8 6.2%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaskan Native	1 0.8%
Asian	1 0.8%
Black or African American	6 4.7%
Native Hawaiian or other Pacific Islander	0 0%
White	116 89.9%
Other	1 0.8%
Unknown	2 1.6%
Missing	2 1.6%
Region of Enrollment (participants) [Number]
Hungary	7 5.4%
United States	46 35.7%
Czechia	9 7%
United Kingdom	11 8.5%
Belarus	10 7.8%
Spain	2 1.6%
Canada	9 7%
Belgium	2 1.6%
Italy	21 16.3%
Georgia	1 0.8%
France	6 4.7%
Bulgaria	5 3.9%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) in All Subjects During Treatment With Duvelisib Based on Standard Response.
Description	Summary of Best Overall Response and Overall Response Rate per IRC Assessment (FAS)
Time Frame	Every 8-16 weeks while on treatment with duvelisib; an expected average on-treatment duration of response follow-up of 24 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
Count of Participants [Participants]	59 45.7%

2. Secondary Outcome

Title	Number of Subjects With Treatment- Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values
Description	Treatment-Emergent Adverse Events Occurring in ≥ 10% Subjects, by SOC and PT (FAS)
Time Frame	Every 2-8 weeks; up to 30 days after the last dose of duvelisib.

Outcome Measure Data

Analysis Population Description

Subjects with at Least 1 TEAE

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
Count of Participants [Participants]	128 99.2%

3. Secondary Outcome

Title	Duration of Response
Description	Duration of Response per IRC Full Analysis Set
Time Frame	Every 8-16 weeks; for an average duration of response follow-up of 24 months

Outcome Measure Data

Analysis Population Description

Duration of Response per IRC Full Analysis Set

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
Median (95% Confidence Interval) [months]	9.9

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression Free Survival per IRC Full Analysis Set
Time Frame	Every 8-16 weeks; for an average response / progression follow-up of 24 months

Outcome Measure Data

Analysis Population Description

Kaplan-Meier Event-Free Estimate (95% Confidence Interval)

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
Median (95% Confidence Interval) [months]	8.4

5. Secondary Outcome

Title	Overall Survival
Description	Overall Survival Full Analysis Set
Time Frame	Every 16 weeks; for an average survival follow-up of 24 months

Outcome Measure Data

Analysis Population Description

Overall Survival Full Analysis Set

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
Median (95% Confidence Interval) [months]	18.4

6. Secondary Outcome

Title	PK Plasma Concentrations of Duvelisib and Its Metabolite(s)
Description	Pharmacokinetics - duvelisib concentration (ng/mL) Full Analysis Set
Time Frame	Every 4 weeks for 12 weeks

Outcome Measure Data

Analysis Population Description

Pharmacokinetics - duvelisib and IPI-656 concentration (ng/mL) Full Analysis Set

Arm/Group Title	Duvelisib	IPI-656
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.	IPI-656 concentration (ng/mL) Full Analysis Set
Measure Participants	129	129
C1D15 Predose	414	648
C1D15 1 hour post dose	1175	641
C1D15 4 hours post dose	852	714
C2D1	631	704
C3D1	696	664

7. Secondary Outcome

Title	Time to Response (TTR)
Description	Time to Response per IRC Full Analysis Set
Time Frame	First dose to first documentation of complete or partial response

Outcome Measure Data

Analysis Population Description

Time to Response per IRC Full Analysis Set

Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor Study IPI-145-06 is an open-label, single-arm efficacy and safety study. Subjects received a dose of 25 mg duvelisib BID over the course of 28-day treatment cycles until disease progression or unacceptable toxicity.
Measure Participants	129
<2 months	36 27.9%
2 - <3 months	5 3.9%
3 - <4 months	10 7.8%
4 - <5 months	2 1.6%
5 - <6 months	5 3.9%
>=6 months	1 0.8%

Adverse Events

Time Frame	24 months
Arm/Group Title	Duvelisib
Arm/Group Description	Duvelisib: PI3K Inhibitor
All Cause Mortality
	Duvelisib
	Affected / at Risk (%)	# Events
Total	37/129 (28.7%)
Serious Adverse Events
	Duvelisib
	Affected / at Risk (%)	# Events
Total	74/129 (57.4%)
Blood and lymphatic system disorders
Febrile neutropenia	9/129 (7%)
Pancytopenia	3/129 (2.3%)
Anaemia	2/129 (1.6%)
Thrombocytopenia	2/129 (1.6%)
Lymph node pain	1/129 (0.8%)
Cardiac disorders
Atrial fibrillation	1/129 (0.8%)
Cardiac failure	1/129 (0.8%)
Cardiac failure congestive	1/129 (0.8%)
Coronary artery occlusion	1/129 (0.8%)
Pericarditis	1/129 (0.8%)
Gastrointestinal disorders
Diarrhoea	9/129 (7%)
Colitis	5/129 (3.9%)
Abdominal pain	2/129 (1.6%)
Enterocolitis	2/129 (1.6%)
Vomiting	2/129 (1.6%)
Abdominal mass	1/129 (0.8%)
Duodenitis	1/129 (0.8%)
Enteritis	1/129 (0.8%)
Nausea	1/129 (0.8%)
Oesophagitis	1/129 (0.8%)
Pancreatitis acute	1/129 (0.8%)
General disorders
Disease progression	8/129 (6.2%)
Pyrexia	4/129 (3.1%)
Fatigue	1/129 (0.8%)
Hepatobiliary disorders
Cholecystitis	1/129 (0.8%)
Hyperbilirubinaemia	1/129 (0.8%)
Infections and infestations
Pneumonia	5/129 (3.9%)
Bronchopneumonia	3/129 (2.3%)
Bronchopulmonary aspergillosis	1/129 (0.8%)
Cellulitis	1/129 (0.8%)
Clostridium difficile colitis	1/129 (0.8%)
Cystitis pseudomonal	1/129 (0.8%)
Diverticulitis	1/129 (0.8%)
Escherichia sepsis	1/129 (0.8%)
Gastroenteritis	1/129 (0.8%)
Infective myositis	1/129 (0.8%)
Influenza	1/129 (0.8%)
Klebsiella sepsis	1/129 (0.8%)
Lower respiratory tract infection	1/129 (0.8%)
Neutropenic sepsis	1/129 (0.8%)
Oral candidiasis	1/129 (0.8%)
Oropharyngeal candidiasis	1/129 (0.8%)
Pneumocystis jirovecii pneumonia	1/129 (0.8%)
Pneumonia cytomegaloviral	1/129 (0.8%)
Pneumonia pseudomonas aeruginosa	1/129 (0.8%)
Pseudomembranous colitis	1/129 (0.8%)
Pseudomonal bacteraemia	1/129 (0.8%)
Pseudomonal sepsis	1/129 (0.8%)
Pyelonephritis acute	1/129 (0.8%)
Scrotal infection	1/129 (0.8%)
Sepsis	1/129 (0.8%)
Sepsis syndrome	1/129 (0.8%)
Septic shock	1/129 (0.8%)
Urinary tract infection	1/129 (0.8%)
Viral infection	1/129 (0.8%)
Vulval cellulitis	1/129 (0.8%)
Injury, poisoning and procedural complications
Infusion related reaction	1/129 (0.8%)
Spinal compression fracture	1/129 (0.8%)
Investigations
Alanine aminotransferase increased	1/129 (0.8%)
Blood creatinine increased	1/129 (0.8%)
Metabolism and nutrition disorders
Hypokalaemia	2/129 (1.6%)
Hypercalcaemia	1/129 (0.8%)
Hyperkalaemia	1/129 (0.8%)
Hypoglycaemia	1/129 (0.8%)
Hyponatraemia	1/129 (0.8%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/129 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	2/129 (1.6%)
Acute myeloid leukaemia	1/129 (0.8%)
Malignant Melanoma	1/129 (0.8%)
Myelodysplastic syndrome	1/129 (0.8%)
Neuroendocrine carcinoma of the skin	1/129 (0.8%)
Non-small cell lung cancer	1/129 (0.8%)
Nervous system disorders
Transient ischaemic attack	1/129 (0.8%)
Renal and urinary disorders
Renal failure acute	3/129 (2.3%)
Renal failure	2/129 (1.6%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/129 (2.3%)
Pneumonitis	2/129 (1.6%)
Respiratory disorder	1/129 (0.8%)
Skin and subcutaneous tissue disorders
Rash	2/129 (1.6%)
Rash generalised	2/129 (1.6%)
Dermatitis allergic	1/129 (0.8%)
Dermatitis exfoliative	1/129 (0.8%)
Drug reaction with eosinophilia and systemic symptoms	1/129 (0.8%)
Toxic epidermal necrolysis	1/129 (0.8%)
Vascular disorders
Deep vein thrombosis	1/129 (0.8%)
Embolism	1/129 (0.8%)
Peripheral embolism	1/129 (0.8%)
Superior vena cava syndrome	1/129 (0.8%)
Other (Not Including Serious) Adverse Events
	Duvelisib
	Affected / at Risk (%)	# Events
Total	128/129 (99.2%)
Blood and lymphatic system disorders
Neutropenia	34/129 (26.4%)
Thrombocytopenia	20/129 (15.5%)
Anaemia	28/129 (21.7%)
Gastrointestinal disorders
Diarrhoea	57/129 (44.2%)
Nausea	37/129 (28.7%)
Vomiting	20/129 (15.5%)
Abdominal pain	15/129 (11.6%)
Constipation	15/129 (11.6%)
Dry mouth	9/129 (7%)
Stomatitis	8/129 (6.2%)
General disorders
Fatigue	31/129 (24%)
Pyrexia	26/129 (20.2%)
Oedema peripheral	19/129 (14.7%)
Asthenia	14/129 (10.9%)
Chills	7/129 (5.4%)
Infections and infestations
Oral Candidiasis	7/129 (5.4%)
Investigations
Alanine aminotransferase increased	17/129 (13.2%)
Aspartate aminotransferase increased	13/129 (10.1%)
Lipase increased	11/129 (8.5%)
Weight decreased	9/129 (7%)
Blood alkaline phosphatase increased	7/129 (5.4%)
Blood creatinine increased	7/129 (5.4%)
Neutrophil count decreased	7/129 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	19/129 (14.7%)
Hypokalaemia	15/129 (11.6%)
Dehydration	7/129 (5.4%)
Hyperuricaemia	7/129 (5.4%)
Musculoskeletal and connective tissue disorders
Back pain	17/129 (13.2%)
Arthralgia	16/129 (12.4%)
Pain in extremity	11/129 (8.5%)
Musculoskeletal pain	7/129 (5.4%)
Nervous system disorders
Headache	19/129 (14.7%)
Respiratory, thoracic and mediastinal disorders
Cough	31/129 (24%)
Dyspnoea	10/129 (7.8%)
Oropharyngeal pain	8/129 (6.2%)
Skin and subcutaneous tissue disorders
Rash	21/129 (16.3%)
Night sweats	11/129 (8.5%)
Pruritus	11/129 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.