Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas

Phase 2

Completed

Conditions: Follicular Lymphoma
Lymphoplasmacytic Lymphoma
Marginal Zone Lymphoma
Small Lymphocytic Lymphoma

Interventions: Drug: Idelalisib

Registration Number: NCT01282424

Lead Sponsor: Gilead Sciences

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 125

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Idelalisib	Idelalisib	Treatment with idelalisib will be continued until tumor progression or development of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Start of Treatment to End of Treatment (up to 81 months)	Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response \[MR\] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)

Secondary Outcome Measures

Name	Time	Method
Duration of Response	Start of Treatment to End of Treatment (up to 81 months)	Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms	Start of Treatment to End of Treatment (up to 81 months) plus 30 days	This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.
Time to Response	Start of Treatment to End of Treatment (up to 81 months)	Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.
Change in Karnofsky Performance Status	Baseline to End of Treatment (up to 81 months)	The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.
Lymph Node Response Rate	Start of Treatment to End of Treatment (up to 81 months)	Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.
Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)	Baseline to End of Treatment (up to 81 months)	Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.
PK Parameter: AUClast	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29	AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration
Overall Survival	Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)	Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.
Study Drug Exposure	Start of Treatment to End of Treatment (up to 81 months)	The average idelalisib exposure was summarized.
Idelalisib Plasma Concentration	Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
PK Parameter: Cmax	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29	Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.
Progression-Free Survival	Start of Treatment to End of Treatment (up to 81 months)	Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.
PK Parameter: Tmax	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29	Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).
Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines	Enrollment to End of Treatment (up to 81 months)	Analysis of the cytokine/chemokine was planned to be performed on a subset of samples from this study along with a subset of samples from other studies. Therefore, data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Trial Locations

Locations (41): St. Jude Medical Center
🇺🇸
Fullerton, California, United States
University of Medicine and Dentistry of NJ
🇺🇸
New Brunswick, New Jersey, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Małopolskie Centrum Medyczne
🇵🇱
Kraków, Poland
Central Coast Medical Oncology
🇺🇸
Santa Maria, California, United States
Stanford Cancer Center
🇺🇸
Stanford, California, United States
University of Virginia Medical Center
🇺🇸
Charlottesville, Virginia, United States
Sarah Cannon Institute
🇬🇧
London, United Kingdom
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Universitatsklinikum Ulm
🇩🇪
Ulm, Germany
Centrum Onkologii w Warszawie
🇵🇱
Warsaw, Poland
Centre Henri Bequerel
🇫🇷
Rouen, France
Universitätsklinikum Essen
🇩🇪
Essen, Germany
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Collaborative Research Group, LLC
🇺🇸
Boynton Beach, Florida, United States
Chattanooga Hem/Oncology Ass (SCRI)
🇺🇸
Chattanooga, Tennessee, United States
St James's Institute of Oncology
🇬🇧
Leeds, United Kingdom
The Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
The Christie Hospital
🇬🇧
Manchester, United Kingdom
Klinikum der Universität München-Großhadern
🇩🇪
München, Germany
Southampton General Hospital
🇬🇧
Southampton, United Kingdom
John Theurer Cancer Center Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
🇮🇹
Bologna, Italy
A.O.U. San Martino
🇮🇹
Genova, Italy
Fondazione Centro San Raffaele del Monte Tabor
🇮🇹
Milano, Italy
CHU Morvan
🇫🇷
Brest, France
Centre Hospitalier de Lyon Sud
🇫🇷
Pierre Benite, France
Università "Sapienza"
🇮🇹
Rome, Italy
CHU Bretonneau - Centre Kaplan
🇫🇷
Tours, France
Charité Campus Virchow Klinikum
🇩🇪
Berlin, Germany
Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Pacific Shores Medical Group
🇺🇸
Long Beach, California, United States
UCLA
🇺🇸
Los Angeles, California, United States
Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Weill Cornell -New York Presbyterian Hospital
🇺🇸
New York, New York, United States
South Carolina Oncology Associates
🇺🇸
Columbia, South Carolina, United States
St Bartholemews Hospital
🇬🇧
London, United Kingdom
Montefiore Medical Center
🇺🇸
New York, New York, United States