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

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

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.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Idelalisib

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Brest, France, 29609
    • CHU Morvan
  • Pierre Benite, France, 69310
    • Centre Hospitalier de Lyon Sud
  • Rouen, France, 76038
    • Centre Henri Bequerel
  • Tours, France, 37044
    • CHU Bretonneau - Centre Kaplan
• Germany
  • Berlin, Germany, 13353
    • Charite Campus Virchow Klinikum
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
  • München, Germany, 81377
    • Klinikum der Universität München-Großhadern
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
  • Genova, Italy, 16132
    • A.O.U. San Martino
  • Milano, Italy, 20132
    • Fondazione Centro San Raffaele del Monte Tabor
  • Rome, Italy, 00161
    • Università "Sapienza"
• Poland
  • Kraków, Poland, 30-510
    • Małopolskie Centrum Medyczne
  • Warsaw, Poland, 02-781
    • Centrum Onkologii w Warszawie
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James's Institute of Oncology
  • London, United Kingdom, EC1M 6BQ
    • St Bartholemews Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Institute
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • Long Beach, California, United States, 90813-3244
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90095
      • UCLA
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology
    • Stanford, California, United States, 94035-5796
      • Stanford Cancer Center
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Collaborative Research Group, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Robert H. Lurie Comprehensive Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08901-1914
      • University of Medicine and Dentistry of NJ
  • New York
    • New York, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10002
      • Weill Cornell -New York Presbyterian Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Hem/Oncology Ass (SCRI)
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Charles A. Sammons Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-5156
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idelalisib; Treatment with idelalisib will be continued until tumor progression or development of unacceptable toxicity.	Drug: Idelalisib; Idelalisib 150 mg tablet administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; IDELA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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)	Start of Treatment to End of Treatment (up to 81 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	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.	Start of Treatment to End of Treatment (up to 81 months)
Lymph Node Response Rate	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.	Start of Treatment to End of Treatment (up to 81 months)
Time to Response	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.	Start of Treatment to End of Treatment (up to 81 months)
Progression-Free Survival	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.	Start of Treatment to End of Treatment (up to 81 months)
Overall Survival	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.	Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)
Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)	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.	Baseline to End of Treatment (up to 81 months)
Change in Karnofsky Performance Status	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.	Baseline to End of Treatment (up to 81 months)
Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines	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.	Enrollment to End of Treatment (up to 81 months)
Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms	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.	Start of Treatment to End of Treatment (up to 81 months) plus 30 days
Study Drug Exposure	The average idelalisib exposure was summarized.	Start of Treatment to End of Treatment (up to 81 months)
Idelalisib Plasma Concentration		Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
PK Parameter: Cmax	Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
PK Parameter: Tmax	Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
PK Parameter: AUClast	AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2011
• Primary Completion (Actual): May 2, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: January 21, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 25, 2011

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: NHL; Non-Hodgkin Lymphoma; Small lymphocytic lymphoma (SLL); CAL-101; GS-1101; PI3K; Follicular Lymphoma (FL); iNHL; indolent Non-Hodgkin Lymphoma; Phosphatidylinositol 3-kinase; Lymphoplasmacytoid lymphoma (LPL); Marginal zone lymphoma (MZL)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Idelalisib
• Other Study ID Numbers: 101-09; 2010-022155-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No