Safety and Efficacy of Idelalisib in Relapsed or Refractory Hodgkin Lymphoma

A Phase 2 Study to Assess the Efficacy and Safety of GS-1101 (CAL-101) in Patients With Relapsed or Refractory Hodgkin Lymphoma

This study will evaluate the efficacy and safety of idelalisib in participants with relapsed of refractory Hodgkin Lymphoma (HL). The primary objective will be to assess the overall response rate.

Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg twice daily. Treatment with idelalisib will continue until tumor progression or unacceptable toxicity.

Study Overview

• Status: Completed
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: Idelalisib

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 12 years
• Karnofsky performance score of ≥ 60 (Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2)
• Histologically confirmed diagnosis of classic HL (ie, nodular sclerosis, mixed cellularity, lymphocyte depleted, and or lymphocyte rich types)
• Nodal HL that shows fluorodeoxyglucose (FDG) avidity (defined as focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology), and is measurable (defined as the presence of ≥ 1 nodal lesion that measures ≥ 2 cm in a single dimension as assessed by CT, PET/CT, or magnetic resonance imaging (MRI))
• Relapsed or refractory HL after prior myeloablative therapy with autologous stem cell transplantation (ASCT) or after ≥ 2 prior chemotherapy-containing regimens and no curative option with conventional therapy
• Discontinuation of all radiotherapy or chemotherapy for the treatment of HL greater than or equal to 3 weeks before initiation of study treatment and discontinuation of all radioimmunotherapy for HL (Visit 2)
• All acute toxic effects (excluding alopecia, neurotoxicity, or anemia) of any prior antitumor therapy resolved to Grade ≤ 2 before initiation of study treatment (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 protocol requirements

Exclusion Criteria:

• Known active central nervous system or leptomeningeal 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 (Visit 2)
• Pregnancy or breastfeeding
• Ongoing alcohol or drug addiction
• Known history of drug-induced liver injury, chronic active hepatitis C virus (HCV), chronic active hepatitis B virus (HBV), 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.
• 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 patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results
• Prior therapy with any drug that inhibits Akt, Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3 kinase (PI3K) (including idelalisib), or spleen tyrosine kinase (SYK)

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; Participants will receive up to 300 mg of idelalisib twice daily.	Drug: Idelalisib; Idelalisib tablets administered orally; Other Names: Zydelig®; GS-1101; CAL-101

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 proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator.; 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.	Up to Week 110

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 PR or CR to the earlier of the first documentation of disease progression or death from any cause.	Up to Week 110
Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of Target Lymph Nodes as Documented Radiographically		Baseline, Week 8, Week 48, and up to Week 110
Change From Baseline in Fluorodeoxyglucose (FDG) Uptake in Lymph Nodes as Assessed by Positron-emission Tomography (PET)		Up to Week 110
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.	Up to Week 110
Overall Survival	Overall survival was defined as the time from start of idelalisib treatment to death from any cause.	Up to Week 110
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 or death from any cause.	Up to Week 110
Time to Treatment Failure	Time to treatment failure (TTF) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression, the permanent cessation of idelalisib therapy due to an adverse event, or death from any cause.	Up to Week 110
Changes in Health-related Quality of Life as Reported Using the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym) Questionnaire	Change in health-related quality of life was reported by participants using the FACT-Lym questionnaire assessment tool. Results are presented as the mean (SD) best change from baseline in FACT-Lym total score, which was defined as the highest change score (improvement) after baseline. The FACT-Lym total score is on a scale from 0-168, with higher scores associated with a better quality of life.	Baseline and up to Week 110
Changes in Performance Status as Documented Using the Karnofsky Performance Criteria for Participants ≥ 16 Years of Age and the Lansky Performance Criteria for Participants < 16 Years of Age	Changes in performance status were assessed using the Karnofsky performance criteria for participants ≥ 16 years of age and the Lansky performance criteria for participants < 16 years of age. Since there were no participants < 16 years of age, only the Karnofsky performance criteria were used. 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 classifies patients 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 and up to Week 110
Changes in the Plasma Concentrations of Disease-associated Chemokines and Cytokines		Up to Week 110
Overall Safety Profile of Idelalisib	The overall safety of idelalisib was assessed as the percentage of participants experiencing adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib), clinically significant abnormal electrocardiograms (ECG), and laboratory abnormalities. "Clinically significant" abnormalities in ECG were as determined by the investigator.	Up to Week 110
Compliance With Study Drug Dosing as Assessed by Accounting for Used and Unused Drug		Up to Week 110
Idelalisib Trough and Peak Plasma Concentration at Week 4	Plasma samples were collected predose (trough) and 1.5 hours postdose (peak). The minimum and maximum value among participants sampled at each time point are presented. Results of less than the lower limit of quantitation (ie, 5 ng/mL) were treated as zero prior to the achievement of the first quantifiable concentration and as missing otherwise.	Predose and 1.5 hours postdose at Week 4

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Lyndah Dreiling, MD, Gilead Sciences

Publications and helpful links

General Publications

• Gopal AK, Fanale MA, Moskowitz CH, Shustov AR, Mitra S, Ye W, Younes A, Moskowitz AJ. Phase II study of idelalisib, a selective inhibitor of PI3Kdelta, for relapsed/refractory classical Hodgkin lymphoma. Ann Oncol. 2017 May 1;28(5):1057-1063. doi: 10.1093/annonc/mdx028.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: HL; CAL-101; GS-1101; PI3K; idelalisib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Idelalisib
• Other Study ID Numbers: 101-11

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)