Dose Optimization Study of Idelalisib in Follicular Lymphoma

Sponsor
Gilead Sciences (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02536300
Collaborator
(none)
96
66
3
177.6
1.5
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
96 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
As of protocol amendment 5, the Idelalisib 100 mg arm is closed to enrollment.As of protocol amendment 5, the Idelalisib 100 mg arm is closed to enrollment.
Masking:
None (Open Label)
Masking Description:
Double-blind: Prior to protocol amendment 5; Open-label: Participants enrolled as of protocol amendment 5
Primary Purpose:
Treatment
Official Title:
Dose Optimization Study of Idelalisib in Follicular Lymphoma
Actual Study Start Date :
Jan 14, 2016
Anticipated Primary Completion Date :
Nov 1, 2025
Anticipated Study Completion Date :
Nov 1, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idelalisib 150 mg Continuously

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 tablet administered orally
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
  • Experimental: Idelalisib 100 mg

    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 tablet administered orally
    Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
  • Experimental: Idelalisib 150 mg 28-Day Cycles

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

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Up to end of radiographic assessment (approximately Week 84)]

      ORR is defined as the proportion of participants who achieve a partial response (PR) or complete response (CR).

    2. Incidence of Grade ≥ 4 Treatment-Emergent Adverse Events (TEAEs) [Up to end of study (approximately 10 years)]

    Secondary Outcome Measures

    1. Duration of Response (DOR) [Up to end of radiographic assessment (approximately Week 84)]

      DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression by IRC or death from any cause.

    2. Overall Response Rate by Week 24 [Up to Week 24]

      ORR by Week 24 is defined as the proportion of participants who achieve a PR or CR by Week 24.

    3. Overall Safety Profile of Idelalisib [Up to end of study (approximately 10 years)]

      The overall safety profile of idelalisib will include the incidence of adverse events (AE), clinically significant laboratory abnormalities, ≥ Grade 3 AEs, idelalisib-related AEs, serious adverse events (SAEs), and AEs leading to interruption, reduction, or discontinuation of idelalisib.

    4. Time to onset of adverse events of interest (AEI) [Up to end of study (approximately 10 years)]

      Time to onset of AEI is defined as the interval from the start of idelalisib treatment to the first documentation of start of AEI.

    5. Progression-Free Survival (PFS) [Up to end of radiographic assessment (approximately Week 84)]

      PFS is defined as the interval from randomization to the earlier of the first documentation of disease progression by IRC or death from any cause.

    6. Overall Survival (OS) [Up to end of study (approximately 10 years)]

      OS is defined as the interval from randomization to death from any cause.

    7. Idelalisib Trough (pre-dose) and Peak (1.5-hour samples) Plasma Concentrations [Predose and 1.5 hours postdose in the morning up to Week 48]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Calvary Norht Adelaide Hosptial Woodville South South Australia Australia 5011
    2 Royal Victoria Regional Health Centre Barrie Canada L4M 6M2
    3 Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika Brno Czechia 625 00
    4 Fakultni nemocnice Kralovske Vinohrady Prague 10 Czechia 10034
    5 Fakulni newmcince v Motole, Onkologicka klinika 2. LF UK a FN Motol Praha 5 Czechia 150 06
    6 Centre Hospitalier d'Avignon-Hopital Henri Duffaut Avignon France 84000
    7 Polyclinique Bordeaux Nord Aquitaine Bordeaux France 33077
    8 Centre Hospitalier Le Mans Le Mans France 72037
    9 Hopital Saint Louis Paris Cedex 10 France 75475
    10 Hopital Saint Antoine Paris cedex 12 France 72012
    11 Centre Hospitalier Universaitaire de Poit iers-Pole Regional de Cancerlogie Poitiers Cedex France 86021
    12 Centre Hospitalier de Tours-Hopital Bretoneau Centre Regional de Cancerologie Henry Kaplan Tours Cedex France 37044
    13 Clinique Louis Pasteur Vandoeuvre-lés-Nancy France 54511
    14 Carmel Medical Center Haifa Israel 34362
    15 Meir Medical Center Kfar Saba Israel 4428164
    16 Azienda Ospedaliera Papa Giovanni XXIII Bergamo Italy 24127
    17 ASST Spedali Civili Brescia Italy 25123
    18 Ospedale Policlinico San Martino IRCCS-Clinica Ematologica Genoa Italy 16132
    19 Azienda Policlinico San Martino Genova Italy 16132
    20 Azienda Ospedaliera Cardinale G Panico di Tricase-Unita Operativa Complessa di Ematologia e TMO Lecce Italy 73039
    21 Azienda Ospedaliera Vito Fazzi Unita Operativa di Ematologia Lecce Italy 73100
    22 Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Dipartimento di Oncologia Medica Meldola Italy 47014
    23 IRCCS Ospendale San Raffaele Milano Italy 20132
    24 SCDU Ematologia e Terapie Cellulari Azienda Ospedaliera Ordine Mauriziano di Torino Orbassano Italy 10043
    25 Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello Palermo Italy 90146
    26 Azienda Unita Sanitaria Locale di Ravenna, U.O di Ematologia Ravenna Italy 48121
    27 Ospedale degli Infermi-Oncoematologia Rimini Italy 47900
    28 Fondazione Policlinico Tor Vergata-UOC Patologie Linfoproliferative Rome Italy 00133
    29 Ospedale S. Eugenio Rome Italy 00144
    30 Dipartimento di Ematologia ed Oncoematolgia - S.C Ematolgia Torino Italy 10126
    31 A.S.U. Integrata Santa Maria della Misericordia Udine Italy 33100
    32 Szpitale Wojewodzkie w Gdyni Sp. z o.o. Gdynia Poland 81-519
    33 PRATIA Onkologia Katowice Katowice Poland 40-519
    34 Malopolskie Centrum Medyczne Kraków Poland 30-510
    35 Wojewodzki Szpital Specjalistyczny w Legniicy Legnica Poland 59-220
    36 Gabinety Lekarskie Hema Lublin Poland 20-090
    37 Szpital Wojewodzki w Opolu Sp. z o.o. Opole Poland 45-372
    38 Instytut Hematologii i Transfuzjologii, Klinika Hematologii Warszawa Poland 02-776
    39 Centrum Onkologii Instytut im.Marii Sklodowskiej Curie Warszawa Poland 02-781
    40 Klinika Hematologii Nowotworow Kriwi i Transplantacji Szpiku Wroclaw Poland 50-367
    41 Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare Baia Mare Romania 430031
    42 Hospital del Mar Barcelona Spain 08003
    43 Hospital Universitario de Burgos Burgos Spain 09006
    44 Hospital San Pedro de Alcantara Cáceres Spain 10003
    45 Institut Catala d'Oncologia Hospital Universitari de Bellvitge L'Hospitalet de Llobregat Spain 08908
    46 Hospital General Universiario Gregorio Maranon Madrid Spain 28009
    47 Hospital Universitario Infanta Leonor Madrid Spain 28031
    48 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    49 Fundacion Jimenez Diaz Madrid Spain 28040
    50 Centro Integral Oncologico Clara Campal (CIOCC) Madrid Spain 28050
    51 Hospital Puerta de Hierro Majadahonda Majadahonda Spain 28222
    52 Hospital Genereal Universitario Morales Meseguer Murcia Spain 30008
    53 Hospital Son Llatzer Palma de Mallorca Spain 07198
    54 Hospital Universitario de Canarias Santa Cruz de Tenerife Spain 38320
    55 Hospital Universitario Marques de Valdecilla Santander Spain 39008
    56 Hospital Universitario Mutua Terrassa Terrassa Spain 08221
    57 CEIm-Regional De La Comunidad De Madrid Valencia Spain 46026
    58 Hospital Clinico Universitario Lozano Blesa Zaragoza Spain 50009
    59 East Kent Hospitals University NHS Foundation Trust Canterbury United Kingdom CT1 3NG
    60 London North West University Healthcare NHS Trust Harrow United Kingdom HA1 3UJ
    61 Clatterbridge Cancer Centre NHS Foundation Trust Liverpool United Kingdom L7 8XP
    62 Barts Health Trust London United Kingdom EC1A7BE
    63 University College London Hospitals NHS Foundation Trust London United Kingdom NW1 2PG
    64 St George's Hospital NHS Trust London United Kingdom SW17 0QT
    65 The Pennine Acute Hospital NHS Trust Oldham United Kingdom OL1 2JH
    66 Torbay and South Devon NHS Foundation Trust Torquay United Kingdom TQ2 7AA

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02536300
    Other Study ID Numbers:
    • GS-US-313-1580
    • 2015-000366-66
    First Posted:
    Aug 31, 2015
    Last Update Posted:
    Aug 25, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 25, 2022