Dose Optimization Study of Idelalisib in Follicular Lymphoma
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 |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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).
- Incidence of Grade ≥ 4 Treatment-Emergent Adverse Events (TEAEs) [Up to end of study (approximately 10 years)]
Secondary Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
- Overall Survival (OS) [Up to end of study (approximately 10 years)]
OS is defined as the interval from randomization to death from any cause.
- 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
Key Inclusion Criteria:
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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
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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.
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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)
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Required baseline central laboratory data in protocol.
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For female individuals of childbearing potential and male individuals of reproductive potential, willingness to use a protocol- recommended method of contraception
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Lactating females must agree to discontinue nursing
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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:
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History of lymphoid malignancy other than FL (eg, diffuse large B-cell lymphoma)
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Known history of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma.
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Known presence of intermediate- or high-grade myelodysplastic syndrome.
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Known history of serious allergic reaction including anaphylaxis or Stevens- Johnson syndrome/ toxic epidermal necrolysis
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History of a non-lymphoid malignancy except for protocol allowed exceptions
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Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
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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
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History of or ongoing drug-induced pneumonitis
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History of or ongoing inflammatory bowel disease
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Known human immunodeficiency virus (HIV) infection
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History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
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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
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Concurrent participation in another therapeutic clinical trial
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Prior treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors
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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 | |
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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.- GS-US-313-1580
- 2015-000366-66