Clinical trial NCT02536300: Dose Optimization Study of Idelalisib in Follicular Lymphoma
Official title: Dose Optimization Study of Idelalisib in Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Follicular Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-08-31
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: As of protocol amendment 5, the Idelalisib 100 mg arm is closed to enrollment.
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to establish a safe and effective dosing regimen of idelalisib in participants with relapsed or refractory follicular lymphoma (FL) who have no other therapeutic options.


Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed diagnosis of B-cell follicular lymphoma (FL), and grade limited to 1, 2, or 3a based on criteria established by the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissues
* Relapsed or refractory FL and have received at least 2 lines of prior therapy for FL and have no other available therapeutic options. Note: Rituximab maintenance is not routinely considered a separate line of therapy when it is given as part of the prior rituximab-containing regimen given over a number of cycles followed by maintenance. Rituximab monotherapy may be considered a separate line of therapy when disease relapse occurs between the initiation of rituximab monotherapy and the preceding line of therapy. If there are any ambiguities about eligibility, the site should consult with the medical monitor.
* Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease per Lugano Classification Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 1.5 cm in the longest dimension (LD) and ≥ 1.0 cm in the longest perpendicular dimension (LPD) as assessed by positron emission tomography-computed tomography (PET-CT), computed tomography (CT) or magnetic resonance imaging (MRI)
* Required baseline central laboratory data in protocol.
* For female individuals of childbearing potential and male individuals of reproductive potential, willingness to use a protocol- recommended method of contraception
* Lactating females must agree to discontinue nursing
* Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions including mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP)

Key Exclusion Criteria:

* History of lymphoid malignancy other than FL (eg, diffuse large B-cell lymphoma)
* Known history of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma.
* Known presence of intermediate- or high-grade myelodysplastic syndrome.
* Known history of serious allergic reaction including anaphylaxis or Stevens- Johnson syndrome/ toxic epidermal necrolysis
* History of a non-lymphoid malignancy except for protocol allowed exceptions
* Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
* Known history of drug-induced liver injury, chronic active hepatitis B virus (HBV), chronic active hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasis
* History of or ongoing drug-induced pneumonitis
* History of or ongoing inflammatory bowel disease
* Known human immunodeficiency virus (HIV) infection
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy, including systemic corticosteroids (\> 10 mg prednisone or equivalent/day) with the exception of the use of topical, enteric, or inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for autoimmune anemia and/or thrombocytopenia
* Concurrent participation in another therapeutic clinical trial
* Prior treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors
* Cytomegalovirus (CMV): Ongoing infection, treatment, or specifically CMV antiviral prophylaxis within 28 days prior to the screening visits CMV test

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Randomization up to end of treatment (maximum duration: 73.5 months)
measure: Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months)
measure: Overall Response Rate (ORR) by Week 24
timeFrame: First dose date up to Week 24
measure: Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib
timeFrame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
measure: Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
measure: Time to Onset of Adverse Events of Interest (AEIs)
timeFrame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
measure: Progression-Free Survival (PFS)
timeFrame: Randomization up to PD or death from any cause (maximum duration: 73.5 months)
measure: Overall Survival (OS)
timeFrame: Randomization up to death from any cause (maximum duration: 73.5 months)
measure: Trough Plasma Concentration of Idelalisib
timeFrame: Predose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48
measure: Peak Plasma Concentration of Idelalisib
timeFrame: 1.5 hours postdose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48
Other outcomes:
Locations:
city: Woodville South
country: Australia
facility: Calvary Norht Adelaide Hosptial
state: South Australia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika
city: Prague 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 5
country: Czechia
facility: Fakulni newmcince v Motole, Onkologicka klinika 2. LF UK a FN Motol
city: Avignon
country: France
facility: Centre Hospitalier d'Avignon-Hopital Henri Duffaut
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Paris Cedex 10
country: France
facility: Hopital Saint Louis
city: Paris cedex 12
country: France
facility: Hopital Saint Antoine
city: Poitiers Cedex
country: France
facility: Centre Hospitalier Universaitaire de Poit iers-Pole Regional de Cancerlogie
city: Tours Cedex
country: France
facility: Centre Hospitalier de Tours-Hopital Bretoneau Centre Regional de Cancerologie Henry Kaplan
city: Vandoeuvre-lés-Nancy
country: France
facility: Clinique Louis Pasteur
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Brescia
country: Italy
facility: ASST Spedali Civili
city: Genoa
country: Italy
facility: Ospedale Policlinico San Martino IRCCS-Clinica Ematologica
city: Genova
country: Italy
facility: Azienda Policlinico San Martino
city: Lecce
country: Italy
facility: Azienda Ospedaliera Cardinale G Panico di Tricase-Unita Operativa Complessa di Ematologia e TMO
city: Lecce
country: Italy
facility: Azienda Ospedaliera Vito Fazzi Unita Operativa di Ematologia
city: Meldola
country: Italy
facility: Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Dipartimento di Oncologia Medica
city: Milano
country: Italy
facility: IRCCS Ospendale San Raffaele
city: Orbassano
country: Italy
facility: SCDU Ematologia e Terapie Cellulari Azienda Ospedaliera Ordine Mauriziano di Torino
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale di Ravenna, U.O di Ematologia
city: Rimini
country: Italy
facility: Ospedale degli Infermi-Oncoematologia
city: Rome
country: Italy
facility: Fondazione Policlinico Tor Vergata-UOC Patologie Linfoproliferative
city: Rome
country: Italy
facility: Ospedale S. Eugenio
city: Torino
country: Italy
facility: Dipartimento di Ematologia ed Oncoematolgia - S.C Ematolgia
city: Udine
country: Italy
facility: A.S.U. Integrata Santa Maria della Misericordia
city: Gdynia
country: Poland
facility: Szpitale Wojewodzkie w Gdyni Sp. z o.o.
city: Katowice
country: Poland
facility: PRATIA Onkologia Katowice
city: Kraków
country: Poland
facility: Malopolskie Centrum Medyczne
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Legniicy
city: Lublin
country: Poland
facility: Gabinety Lekarskie Hema
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu Sp. z o.o.
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii, Klinika Hematologii
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im.Marii Sklodowskiej Curie
city: Wroclaw
country: Poland
facility: Klinika Hematologii Nowotworow Kriwi i Transplantacji Szpiku
city: Baia Mare
country: Romania
facility: Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital General Universiario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC)
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: Murcia
country: Spain
facility: Hospital Genereal Universitario Morales Meseguer
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Terrassa
country: Spain
facility: Hospital Universitario Mutua Terrassa
city: Valencia
country: Spain
facility: CEIm-Regional De La Comunidad De Madrid
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
city: Harrow
country: United Kingdom
facility: London North West University Healthcare NHS Trust
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's Hospital NHS Trust
city: Oldham
country: United Kingdom
facility: The Pennine Acute Hospital NHS Trust
city: Torquay
country: United Kingdom
facility: Torbay and South Devon NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: