Dose Optimization Study of Idelalisib in Follicular Lymphoma

Follicular Lymphoma Clinical Trial

Official title:

Dose Optimization Study of Idelalisib in Follicular Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02536300
• Other study ID #: GS-US-313-1580
• Secondary ID: 2015-000366-66
• Status: Terminated
• Phase: Phase 3
• Start date: January 14, 2016
• Est. completion date: September 27, 2022

Study information

• Verified date: August 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 96
• Est. completion date: September 27, 2022
• Est. primary completion date: September 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Idelalisib
Idelalisib tablet administered orally

Locations

Country	Name	City	State
Australia	Calvary Norht Adelaide Hosptial	Woodville South	South Australia
Canada	Royal Victoria Regional Health Centre	Barrie
Czechia	Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika	Brno
Czechia	Fakultni nemocnice Kralovske Vinohrady	Prague 10
Czechia	Fakulni newmcince v Motole, Onkologicka klinika 2. LF UK a FN Motol	Praha 5
France	Centre Hospitalier d'Avignon-Hopital Henri Duffaut	Avignon
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Centre Hospitalier Le Mans	Le Mans
France	Hopital Saint Louis	Paris Cedex 10
France	Hopital Saint Antoine	Paris cedex 12
France	Centre Hospitalier Universaitaire de Poit iers-Pole Regional de Cancerlogie	Poitiers Cedex
France	Centre Hospitalier de Tours-Hopital Bretoneau Centre Regional de Cancerologie Henry Kaplan	Tours Cedex
France	Clinique Louis Pasteur	Vandoeuvre-lés-Nancy
Israel	Carmel Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	ASST Spedali Civili	Brescia
Italy	Ospedale Policlinico San Martino IRCCS-Clinica Ematologica	Genoa
Italy	Azienda Policlinico San Martino	Genova
Italy	Azienda Ospedaliera Cardinale G Panico di Tricase-Unita Operativa Complessa di Ematologia e TMO	Lecce
Italy	Azienda Ospedaliera Vito Fazzi Unita Operativa di Ematologia	Lecce
Italy	Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Dipartimento di Oncologia Medica	Meldola
Italy	IRCCS Ospendale San Raffaele	Milano
Italy	SCDU Ematologia e Terapie Cellulari Azienda Ospedaliera Ordine Mauriziano di Torino	Orbassano
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello	Palermo
Italy	Azienda Unita Sanitaria Locale di Ravenna, U.O di Ematologia	Ravenna
Italy	Ospedale degli Infermi-Oncoematologia	Rimini
Italy	Fondazione Policlinico Tor Vergata-UOC Patologie Linfoproliferative	Rome
Italy	Ospedale S. Eugenio	Rome
Italy	Dipartimento di Ematologia ed Oncoematolgia - S.C Ematolgia	Torino
Italy	A.S.U. Integrata Santa Maria della Misericordia	Udine
Poland	Szpitale Wojewodzkie w Gdyni Sp. z o.o.	Gdynia
Poland	PRATIA Onkologia Katowice	Katowice
Poland	Malopolskie Centrum Medyczne	Kraków
Poland	Wojewodzki Szpital Specjalistyczny w Legniicy	Legnica
Poland	Gabinety Lekarskie Hema	Lublin
Poland	Szpital Wojewodzki w Opolu Sp. z o.o.	Opole
Poland	Centrum Onkologii Instytut im.Marii Sklodowskiej Curie	Warszawa
Poland	Instytut Hematologii i Transfuzjologii, Klinika Hematologii	Warszawa
Poland	Klinika Hematologii Nowotworow Kriwi i Transplantacji Szpiku	Wroclaw
Romania	Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare	Baia Mare
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Institut Catala d'Oncologia Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat
Spain	Centro Integral Oncologico Clara Campal (CIOCC)	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital General Universiario Gregorio Maranon	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Puerta de Hierro Majadahonda	Majadahonda
Spain	Hospital Genereal Universitario Morales Meseguer	Murcia
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Universitario de Canarias	Santa Cruz de Tenerife
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Mutua Terrassa	Terrassa
Spain	CEIm-Regional De La Comunidad De Madrid	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury
United Kingdom	London North West University Healthcare NHS Trust	Harrow
United Kingdom	Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Barts Health Trust	London
United Kingdom	St George's Hospital NHS Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Pennine Acute Hospital NHS Trust	Oldham
United Kingdom	Torbay and South Devon NHS Foundation Trust	Torquay

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Australia,  Canada,  Czechia,  France,  Israel,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	ORR was defined as percentage of participants who achieve a partial response (PR) or complete response (CR). PR criteria: No evidence of new disease, a =50% decrease from baseline in sum of products of diameters (SPD) of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. Persistence of bone marrow involvement in a participant who meets other criteria for CR based on the disappearance of all nodal and extra-nodal masses. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (=1.5 cm in longest dimension (LD) for large nodes and =1.0 cm in LD, =1.0 cm in longest perpendicular dimension (LPD) for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow.	Randomization up to end of treatment (maximum duration: 73.5 months)
Primary	Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs)	TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.	First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Secondary	Duration of Response (DOR)	DOR: interval from first documentation of CR/PR to earlier of first documentation of disease progression (PD) by independent review committee (IRC)/death from any cause. PR:No evidence of new disease,=50% decrease from baseline in SPD of index lesions,no increase in non-index disease, no increase in liver/spleen size,no new liver/spleen enlargement; Persistence of bone marrow involvement in participant who meets other CR criteria. CR: No evidence of new disease,regression of all index nodal lesions to normal size (large nodes:=1.5 cm in LD;small nodes:=1.0 cm in LD,=1.0 cm in LPD), regression to normal of all nodal non-index disease,disappearance of all detectable extra-nodal index,non-index disease,normal spleen and liver size, no new liver/spleen enlargement; PD: New node of >1.5 cm or >1.0 to =1.5 cm in LD, >1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion,new non-index disease,increase by 50% in SPD of index lesions,LD of individual node/extra-nodal mass.	From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months)
Secondary	Overall Response Rate (ORR) by Week 24	ORR by Week 24 is defined as the percentage of participants who achieve a PR or CR by Week 24.; PR criteria: No evidence of new disease, a 50% decrease from baseline in SPD of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (=1.5 cm in LD for large nodes and =1.0 cm in LD, =1.0 cm in LPD for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow.	First dose date up to Week 24
Secondary	Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib	TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the NCI CTCAE version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants are counted at the highest AE grade experienced.	First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Secondary	Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days. Laboratory abnormalities included hematology and serum chemistry parameters. Clinically significant laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for severity as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). The number of participants with any post-baseline abnormal laboratory value in Grade 1-4 categories are reported.	First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Secondary	Time to Onset of Adverse Events of Interest (AEIs)	Time to onset of AEIs is defined as the interval (in months) from the start of idelalisib treatment to the first documentation of start of AEI. AEIs included grade = 3 diarrhea/colitis, rash, febrile neutropenia, infection, and any grade of: Pneumonitis, bowel perforation, progressive multifocal leukoencephalopathy (PML), Pneumocystis jirovecii pneumonia (PJP), cytomegalovirus (CMV) infection, and organizing pneumonia.	First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Secondary	Progression-Free Survival (PFS)	PFS is defined as the interval (in months) from randomization to the earlier of the first documentation of PD by IRC or death from any cause. PD criteria: New node of >1.5 cm or >1.0 cm to =1.5 cm in LD, >1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion, new non-index disease, increase by 50% in SPD of index lesions, LD of individual node/extra-nodal mass.	Randomization up to PD or death from any cause (maximum duration: 73.5 months)
Secondary	Overall Survival (OS)	OS is defined as the interval (in months) from randomization to death from any cause.	Randomization up to death from any cause (maximum duration: 73.5 months)
Secondary	Trough Plasma Concentration of Idelalisib		Predose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48
Secondary	Peak Plasma Concentration of Idelalisib		1.5 hours postdose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48

External Links

•   Gilead Clinical Trials Website