Clinical trial NCT01282424: Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas
Official title: A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects With Indolent B-Cell Non-Hodgkin Lymphomas Refractory to Rituximab and Alkylating Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Follicular Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma
Marginal Zone Lymphoma
Keywords: indolent Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma
iNHL
NHL
GS-1101
CAL-101
PI3K
Phosphatidylinositol 3-kinase
Follicular Lymphoma (FL)
Small lymphocytic lymphoma (SLL)
Lymphoplasmacytoid lymphoma (LPL)
Marginal zone lymphoma (MZL)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-01-25
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective will be to assess the overall response rate and to evaluate the efficacy and safety of idelalisib (IDELA; GS-1101) in participants with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy.

Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant participants as long as the study is still ongoing and the participants appear to be benefiting from treatment with acceptable safety.


Eligibility criteria: Key Inclusion Criteria:

* Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group \[ECOG\] performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:

  * Follicular lymphoma (FL)
  * Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
  * Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
  * Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
* Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
* Lymphoma that is refractory to rituximab and to an alkylating agent
* Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
* For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with the protocol requirements

Key Exclusion Criteria:

* Central nervous system or leptomeningeal lymphoma
* Known histological transformation from iNHL to diffuse large B-cell lymphoma
* History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
* Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
* Pregnancy or breastfeeding
* Ongoing alcohol or drug addiction
* Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy, including systemic corticosteroids. Participant may be using topical or inhaled corticosteroids.
* Prior therapy with idelalisib
* Exposure to another investigational drug within 3 weeks prior to start of study treatment
* Concurrent participation in another therapeutic treatment trial
* Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results

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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
Secondary outcomes:
measure: Duration of Response
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
measure: Lymph Node Response Rate
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
measure: Time to Response
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
measure: Progression-Free Survival
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
measure: Overall Survival
timeFrame: Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)
measure: Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)
timeFrame: Baseline to End of Treatment (up to 81 months)
measure: Change in Karnofsky Performance Status
timeFrame: Baseline to End of Treatment (up to 81 months)
measure: Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines
timeFrame: Enrollment to End of Treatment (up to 81 months)
measure: Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms
timeFrame: Start of Treatment to End of Treatment (up to 81 months) plus 30 days
measure: Study Drug Exposure
timeFrame: Start of Treatment to End of Treatment (up to 81 months)
measure: Idelalisib Plasma Concentration
timeFrame: Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
measure: PK Parameter: Cmax
timeFrame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
measure: PK Parameter: Tmax
timeFrame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
measure: PK Parameter: AUClast
timeFrame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Boynton Beach
country: United States
facility: Collaborative Research Group, LLC
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: University of Medicine and Dentistry of NJ
state: New Jersey
city: New York
country: United States
facility: Weill Cornell -New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Hem/Oncology Ass (SCRI)
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Charles A. Sammons Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Brest
country: France
facility: CHU Morvan
city: Pierre Benite
country: France
facility: Centre Hospitalier de Lyon Sud
city: Rouen
country: France
facility: Centre Henri Bequerel
city: Tours
country: France
facility: CHU Bretonneau - Centre Kaplan
city: Berlin
country: Germany
facility: Charité Campus Virchow Klinikum
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: München
country: Germany
facility: Klinikum der Universität München-Großhadern
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Bologna
country: Italy
facility: Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
city: Genova
country: Italy
facility: A.O.U. San Martino
city: Milano
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Rome
country: Italy
facility: Università "Sapienza"
city: Kraków
country: Poland
facility: Małopolskie Centrum Medyczne
city: Warsaw
country: Poland
facility: Centrum Onkologii w Warszawie
city: Leeds
country: United Kingdom
facility: St James's Institute of Oncology
city: London
country: United Kingdom
facility: St Bartholemews Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Institute
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Salles GA, Kahl, BS, Wagner-Johnston ND, et al. Interim results from a phase 2 study of PI3Kδ inhibitor idelalisib in patients with relapsed indolent non-Hodgki lymphoma (iNHL) refractory to both rituximab and an alkylating agent. 12th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, June 19-22, 2013 Abstract No: 064bis.
citation: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. doi: 10.1056/NEJMoa1314583. Epub 2014 Jan 22.
citation: Ma S, Chan RJ, Gu L, Xing G, Rajakumaraswamy N, Ruzicka BB, Wagner-Johnston ND. Retrospective Analysis of the Impact of Adverse Event-Triggered Idelalisib Interruption and Dose Reduction on Clinical Outcomes in Patients With Relapsed/Refractory B-Cell Malignancies. Clin Lymphoma Myeloma Leuk. 2021 May;21(5):e432-e448. doi: 10.1016/j.clml.2020.12.016. Epub 2020 Dec 24.
citation: Barrientos JC, Hillmen P, Salles G, Sharman J, Stilgenbauer S, Gurtovaya O, Xing G, Ruzicka B, Bhargava P, Ghia P, Pagel JM. No increased bleeding events in patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma treated with idelalisib. Leuk Lymphoma. 2021 Apr;62(4):837-845. doi: 10.1080/10428194.2020.1845339. Epub 2020 Dec 10.