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

Follicular Lymphoma Clinical Trial

— DELTA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01282424
• Other study ID #: 101-09
• Secondary ID: 2010-022155-33
• Status: Completed
• Phase: Phase 2
• Start date: March 18, 2011
• Est. completion date: May 16, 2018

Study information

• Verified date: June 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: May 16, 2018
• Est. primary completion date: May 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Lymphoplasmacytic Lymphoma
• Marginal Zone Lymphoma
• Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• Idelalisib
Idelalisib 150 mg tablet administered orally twice daily

Locations

Country	Name	City	State
France	CHU Morvan	Brest
France	Centre Hospitalier de Lyon Sud	Pierre Benite
France	Centre Henri Bequerel	Rouen
France	CHU Bretonneau - Centre Kaplan	Tours
Germany	Charité Campus Virchow Klinikum	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum der Universität München-Großhadern	München
Germany	Universitatsklinikum Ulm	Ulm
Italy	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	Università "Sapienza"	Rome
Poland	Malopolskie Centrum Medyczne	Kraków
Poland	Centrum Onkologii w Warszawie	Warsaw
United Kingdom	St James's Institute of Oncology	Leeds
United Kingdom	Sarah Cannon Institute	London
United Kingdom	St Bartholemews Hospital	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Southampton General Hospital	Southampton
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Collaborative Research Group, LLC	Boynton Beach	Florida
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Chattanooga Hem/Oncology Ass (SCRI)	Chattanooga	Tennessee
United States	Northwestern University Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Charles A. Sammons Cancer Center	Dallas	Texas
United States	St. Jude Medical Center	Fullerton	California
United States	John Theurer Cancer Center Hackensack University Medical Center	Hackensack	New Jersey
United States	Pacific Shores Medical Group	Long Beach	California
United States	UCLA	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of Medicine and Dentistry of NJ	New Brunswick	New Jersey
United States	Montefiore Medical Center	New York	New York
United States	Weill Cornell -New York Presbyterian Hospital	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Central Coast Medical Oncology	Santa Maria	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Poland,  United Kingdom, 

References & Publications (2)

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. PI3Kd inhibitio — View Citation

Salles GA, Kahl, BS, Wagner-Johnston ND, et al. Interim results from a phase 2 study of PI3Kd inhibitor idelalisib in patients with relapsed indolent non-Hodgki lymphoma (iNHL) refractory to both rituximab and an alkylating agent. 12th International Confe

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Study Drug Exposure	The average idelalisib exposure was summarized.	Start of Treatment to End of Treatment (up to 81 months)
Secondary	Idelalisib Plasma Concentration		Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
Secondary	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
Secondary	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
Secondary	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