Dose Optimization Study of Idelalisib in Follicular Lymphoma

NCT02536300 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-313-15802015-000366-66
• Study Type: interventional
• Target: 96
• Locations: 10 countries
• Sites: 66

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.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (9)

• Duration of Response (DOR)

  From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months)

• Overall Response Rate (ORR) by Week 24

  First dose date up to Week 24

• Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib

  First dose date up to 30 days after last dose of study drug (maximum 64.6 months)

• Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities

  First dose date up to 30 days after last dose of study drug (maximum 64.6 months)

• Time to Onset of Adverse Events of Interest (AEIs)

  First dose date up to 30 days after last dose of study drug (maximum 64.6 months)

Study Arms (3)

Idelalisib 150 mg BID

EXPERIMENTAL

Participants will receive idelalisib 150 mg twice daily continuously. For participants enrolled prior to protocol amendment 5: Based on the independent review committee (IRC) response assessment, participants may be discontinued from the study or may receive blinded or open-label idelalisib 150 mg twice daily.

Drug: Idelalisib

Idelalisib 100 mg BID

EXPERIMENTAL

Participants will receive idelalisib 100 mg twice daily continuously. Based on the IRC response assessment, participants may either be dose escalated to open-label 150 mg twice daily or maintain blind and continue on idelalisib 100 mg twice daily. As of protocol amendment 5, enrollment to this arm has been closed.

Drug: Idelalisib

Idelalisib 150 mg BID INT

EXPERIMENTAL

Participants will receive idelalisib 150 mg twice daily in 28-day cycles with 21 days on-treatment and 7 days off-treatment.

Drug: Idelalisib

Interventions

Idelalisib DRUG

Idelalisib tablet administered orally

Also known as: Zydelig®, GS-1101, CAL-101

Idelalisib 100 mg BID; Idelalisib 150 mg BID; Idelalisib 150 mg BID INT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (66)

Calvary Norht Adelaide Hosptial

Woodville South, South Australia, 5011, Australia

Location

Royal Victoria Regional Health Centre

Barrie, L4M 6M2, Canada

Location

Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika

Brno, 625 00, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

Fakulni newmcince v Motole, Onkologicka klinika 2. LF UK a FN Motol

Prague, 150 06, Czechia

Location

Centre Hospitalier d'Avignon-Hopital Henri Duffaut

Avignon, 84000, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33077, France

Location

Centre Hospitalier Le Mans

Le Mans, 72037, France

Location

Hopital Saint Antoine

Paris, 72012, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Centre Hospitalier Universaitaire de Poit iers-Pole Regional de Cancerlogie

Poitiers, 86021, France

Location

Centre Hospitalier de Tours-Hopital Bretoneau Centre Regional de Cancerologie Henry Kaplan

Tours, 37044, France

Location

Clinique Louis Pasteur

Vandoeuvre-lés-Nancy, 54511, France

Location

Carmel Medical Center

Haifa, 34362, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

ASST Spedali Civili

Brescia, 25123, Italy

Location

Ospedale Policlinico San Martino IRCCS-Clinica Ematologica

Genoa, 16132, Italy

Location

Azienda Policlinico San Martino

Genova, 16132, Italy

Location

Azienda Ospedaliera Cardinale G Panico di Tricase-Unita Operativa Complessa di Ematologia e TMO

Lecce, 73039, Italy

Location

Azienda Ospedaliera Vito Fazzi Unita Operativa di Ematologia

Lecce, 73100, Italy

Location

Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Dipartimento di Oncologia Medica

Meldola, 47014, Italy

Location

IRCCS Ospendale San Raffaele

Milan, 20132, Italy

Location

SCDU Ematologia e Terapie Cellulari Azienda Ospedaliera Ordine Mauriziano di Torino

Orbassano, 10043, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello

Palermo, 90146, Italy

Location

Azienda Unita Sanitaria Locale di Ravenna, U.O di Ematologia

Ravenna, 48121, Italy

Location

Ospedale degli Infermi-Oncoematologia

Rimini, 47900, Italy

Location

Fondazione Policlinico Tor Vergata-UOC Patologie Linfoproliferative

Rome, 00133, Italy

Location

Ospedale S. Eugenio

Rome, 00144, Italy

Location

Dipartimento di Ematologia ed Oncoematolgia - S.C Ematolgia

Torino, 10126, Italy

Location

A.S.U. Integrata Santa Maria della Misericordia

Udine, 33100, Italy

Location

Szpitale Wojewodzkie w Gdyni Sp. z o.o.

Gdynia, 81-519, Poland

Location

PRATIA Onkologia Katowice

Katowice, 40-519, Poland

Location

Malopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

Wojewodzki Szpital Specjalistyczny w Legniicy

Legnica, 59-220, Poland

Location

Gabinety Lekarskie Hema

Lublin, 20-090, Poland

Location

Szpital Wojewodzki w Opolu Sp. z o.o.

Opole, 45-372, Poland

Location

Instytut Hematologii i Transfuzjologii, Klinika Hematologii

Warsaw, 02-776, Poland

Location

Centrum Onkologii Instytut im.Marii Sklodowskiej Curie

Warsaw, 02-781, Poland

Location

Klinika Hematologii Nowotworow Kriwi i Transplantacji Szpiku

Wroclaw, 50-367, Poland

Location

Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare

Baia Mare, 430031, Romania

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Institut Catala d'Oncologia Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital General Universiario Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Genereal Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Mutua Terrassa

Terrassa, 08221, Spain

Location

CEIm-Regional De La Comunidad De Madrid

Valencia, 46026, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

East Kent Hospitals University NHS Foundation Trust

Canterbury, CT1 3NG, United Kingdom

Location

London North West University Healthcare NHS Trust

Harrow, HA1 3UJ, United Kingdom

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8XP, United Kingdom

Location

Barts Health Trust

London, EC1A7BE, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

St George's Hospital NHS Trust

London, SW17 0QT, United Kingdom

Location

The Pennine Acute Hospital NHS Trust

Oldham, OL1 2JH, United Kingdom

Location

Torbay and South Devon NHS Foundation Trust

Torquay, TQ2 7AA, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

idelalisib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Double-blind: Prior to protocol amendment 5; Open-label: Participants enrolled as of protocol amendment 5
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: As of protocol amendment 5, the Idelalisib 100 mg arm is closed to enrollment.

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: August 31, 2015
• Study Start: January 14, 2016
• Primary Completion: September 27, 2022
• Study Completion: September 27, 2022
• Last Updated: August 14, 2023
• Results First Posted: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

PL (9); FR (8); AU (1); ES (17); GB (8); CZ (3); IT (16); IL (2); CA (1); RO (1)