Clinical trial NCT01882803: A Study of Duvelisib in Participants With Refractory Indolent Non-Hodgkin Lymphoma
Official title: A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Indolent Non-Hodgkin Lymphoma
Keywords: PI3K Inhibitor
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2013-06-20
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a Phase 2 clinical trial to evaluate the safety and efficacy of duvelisib as a monotherapy in participants with indolent non-Hodgkin lymphoma (iNHL) (follicular lymphoma \[FL\], marginal zone lymphoma, or small lymphocytic lymphoma) that was refractory to rituximab and to either chemotherapy or radioimmunotherapy (RIT).

Detailed description: This was an open-label, single-arm safety and efficacy study of duvelisib administered orally to participants who had been diagnosed with iNHL whose disease was refractory to rituximab and to either chemotherapy or RIT.

Approximately 120 participants received 25 milligrams of duvelisib twice daily over the course of 28-day treatment cycles for up to 13 cycles.

After completing 13 treatment cycles of duvelisib, participants continued to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 13 cycles, participants must have had evidence of response (complete response \[CR\] or partial response \[PR\]) or stable disease according to the International Working Group criteria by the end of Cycle 13.

Eligibility criteria: Inclusion Criteria:

* Participants who had been diagnosed with iNHL that had progressed.
* Participants must have exhibited lack of CR or progressive disease (PR) or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT.
* Participants must have had 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 centimeters in at least one dimension by computed tomography (CT), positron emission tomography/CT or magnetic resonance imaging.
* 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 Bruton's tyrosine kinase inhibitor.
* Prior history of allogeneic hematopoietic stem cell transplant.
* 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 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, hepatitis B surface antigen, or hepatitis B core antibodies.
* 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Every 8-16 weeks while on treatment with duvelisib for up to 72 months
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Every 2-8 weeks for up to 73 months
measure: Duration of Response (DOR)
timeFrame: Every 8-16 weeks for up to 72 months
measure: Progression-free Survival (PFS)
timeFrame: Every 8-16 weeks for up to 72 months
measure: Overall Survival (OS)
timeFrame: Every 16 weeks for up to 72 months
measure: Plasma Concentration of Duvelisib and IPI-656
timeFrame: Every 4 weeks for 12 weeks (C1D15: predose, 1 and 4 hours post dose; C2D1 and C3D1: anytime during study visit)
measure: Time to Response (TTR)
timeFrame: First dose to first documentation of complete or partial response (up to 6 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Whittier
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Fort Myers
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Howell
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Rockville Centre
country: United States
state: New York
city: Canton
country: United States
state: Ohio
city: Lawton
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Lynchburg
country: United States
state: Virginia
city: Lesnoy
country: Belarus
state: Minsk Region
city: Brest
country: Belarus
city: Minsk
country: Belarus
city: Vitebsk
country: Belarus
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Toronto
country: Canada
state: Ontario
city: Gatineau
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czechia
city: Ostrava-Poruba
country: Czechia
city: Angers Cedex 09
country: France
city: Bordeaux
country: France
city: Clermont-Ferrand
country: France
city: Marseille
country: France
city: Pierre Benite
country: France
city: Tbilisi
country: Georgia
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Busto Arsizio
country: Italy
city: Genova
country: Italy
city: Meldola
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Orbassano
country: Italy
city: Parma
country: Italy
city: Ravenna
country: Italy
city: Rimini
country: Italy
city: Varese
country: Italy
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Cardiff
country: United Kingdom
city: Chelsea
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
References:
citation: Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. doi: 10.1200/JCO.18.00915. Epub 2019 Feb 11.