A Phase 3 Extension Study of Duvelisib and Ofatumumab in Patients With CLL/SLL Previously Enrolled in Study IPI-145-07

Sponsor

SecuraBio (Industry)

Overall Status

Completed

CT.gov ID

NCT02049515

Collaborator

(none)

Enrollment

Locations

Arms

78.4

Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 monotherapy or ofatumumab monotherapy in subjects with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) who experienced disease progression after treatment with IPI-145 or Ofatumumab in Study IPI-145-07.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Drug: IPI-145 (duvelisib) Drug: Ofatumumab	Phase 3

Detailed Description

This is an open-label, two- arm, extension study designed to enable subjects who have experienced radiologically- confirmed disease progression in Study IPI-145-07 to receive the alternative treatment (either IPI-145 or ofatumumab) than what was received during study IPI-145-07.

Subjects who have previously received ofatumumab in study IPI-145-07 will receive a starting dose of 25 mg IPI-145 BID continuously in a 21 day cycle for Cycle 1 followed by 28- day treatment cycles thereafter for up to 11 cycles or until disease progression, discontinuation from study participation, or start of subsequent therapy, whichever comes first. After completing approximately 11 cycles of treatment with duvelisib, subjects who, in the judgment of the Investigator, may derive benefit from continued treatment may continue to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 11 cycles, subjects must have evidence of response and CLL/SLL requiring treatment according to the IWCLL/IWG by Cycle 12 Day 1.

Subjects who have previously received IPI-145 in study IPI-145-07 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 unless disease progression or unacceptable toxicity occurs. Administration of ofatumumab will not exceed the 12 doses (within 7 cycles).

Study Design

Study Type:

Interventional

Actual Enrollment :

99 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Study of IPI-145 and Ofatumumab in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Previously Enrolled in Study IPI-145-07

Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Jun 12, 2020

Actual Study Completion Date :

Jun 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IPI-145 IPI-145 is administered orally and supplied as 5 mg and 25 mg formulated capsules.	Drug: IPI-145 (duvelisib) 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 Other Names: Arzerra

Arm

Intervention/Treatment

Experimental: IPI-145

IPI-145 is administered orally and supplied as 5 mg and 25 mg formulated capsules.

Drug: IPI-145 (duvelisib)

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

Other Names:

Arzerra

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [Until progressive disease, death, or other anticancer therapy is initiated (up to 6 years)]

Secondary Outcome Measures

Treatment-emergent adverse events (TEAEs) and changes in safety laboratory values [Enrollment through 30 days after the last dose of either IPI-145 or Ofatumumab]
Duration of Response [From the first documentation of response to the first documentation of PD or death due to any cause (up to 6 years)]
Progression-free survival (PFS) [From the first dose of study treatment to the first documentation of PD or death from any cause (up to 6 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
Diagnosis of active CLL or SLL that meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment
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 0-2
Must meet the following laboratory parameters:

Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
Total bilirubin ≤1.5 x ULN
Serum creatinine ≤2.0 x ULN
Hemoglobin ≥8.0 g/dL with or without transfusion support
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 first dose (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:

Discontinued study participation in Verastem-sponsored IPI-145-07 study
Greater than 3 months from confirmed progressive disease on Study IPI-145-07
History of Richter's transformation or prolymphocytic leukemia
Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requires >20 mg daily (QD) of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support
Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative computed tomography (CT) scan or negative diagnostic lumbar puncture prior to first dose
Use of any anticancer medication from documented PD on Study IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms are allowed)
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 Screening and/or Cycle 1 Day 1 (predose))
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 and herpes simplex virus (HSV)
Baseline QT interval corrected with Fridericia's method (QTcF) >480 ms NOTE: this criterion does not apply to subjects with a right or left bundle branch block (BBB)
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
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
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
Subjects to receive duvelisib: Administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A within 2 weeks of starting duvelisib
Major surgery or invasive intervention within 4 weeks prior to first dose
Pregnant or breastfeeding women
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	La Jolla	California	United States	92093-0698
2	Denver	Colorado	United States	80218
3	Fort Myers	Florida	United States	33916
4	Saint Petersburg	Florida	United States	33705
5	Boston	Massachusetts	United States	02114
6	Boston	Massachusetts	United States	02115
7	Saint Louis	Missouri	United States	63130
8	Hackensack	New Jersey	United States	07601
9	New Brunswick	New Jersey	United States	08903
10	New York	New York	United States	10032
11	New York	New York	United States	10065
12	Cincinnati	Ohio	United States	45236
13	Nashville	Tennessee	United States	37203
14	Charlottesville	Virginia	United States	22903
15	Bedford Park		Australia	5042
16	East Melbourne		Australia	3002
17	Melbourne		Australia	3058
18	Linz		Austria	4010
19	Vienna		Austria	1090
20	Wels		Austria	4600
21	Wien		Austria	1130
22	Bruxelles		Belgium	1000
23	Bruxelles		Belgium	1200
24	Gent		Belgium	9000
25	Leuven		Belgium	3000
26	Sint-Niklaas		Belgium	9100
27	Argenteuil Cedex		France	95107
28	Bobigny		France	93009
29	Bordeaux		France	33076
30	Caen		France	14033
31	Clermont Ferrand		France	63100
32	La Roche Sur Yon		France	85025
33	Limoges Cedex		France	87042
34	Nantes		France	44000
35	Rennes		France	35033
36	Vandœuvre-lès-Nancy		France	54511
37	Berlin		Germany	10707
38	Leer		Germany	26789
39	Ulm		Germany	89081
40	Budapest		Hungary	1083
41	Budapest		Hungary	1122
42	Debrecen		Hungary	4032
43	Gyor		Hungary	9024
44	Kaposvár		Hungary	7400
45	Pecs		Hungary	7624
46	Szeged		Hungary	6725
47	Catania		Italy	95124
48	Lecce		Italy	73100
49	Meldola		Italy	47014
50	Milano		Italy	20132
51	Milano		Italy	20162
52	Padova		Italy	35128
53	Ravenna		Italy	48121
54	Rimini		Italy	47923
55	Roma		Italy	00133
56	Auckland		New Zealand	1023
57	Palmerston North		New Zealand	4442
58	Barcelona		Spain	08035
59	Barcelona		Spain	08036
60	Barcelona		Spain	08041
61	Madrid		Spain	28033
62	Madrid		Spain	28050
63	Pamplona		Spain	31008
64	Bournemouth		United Kingdom	BH7 7DW
65	Leeds		United Kingdom	LS9 7TF
66	Manchester		United Kingdom	M20 4BX
67	Nottingham		United Kingdom	NG5 1PB
68	Oxford		United Kingdom	OX3 7JL
69	Sutton		United Kingdom	SM2 5PT