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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01282424
First received: January 21, 2011
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of idelalisib in patients with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy. The primary objective will be to assess the overall response rate.

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


Condition Intervention Phase
Follicular Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma
Marginal Zone Lymphoma
Drug: Idelalisib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects With Indolent B-Cell Non-Hodgkin Lymphoma Refractory to Rituximab and Alkylating Agents

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]

    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 subjects achieving a complete response (CR) or partial response (PR; or minor response [MR] for subjects with Waldenström macroglobulinemia [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 IgM of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; plus any reduction 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:
  • Duration of Response [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Lymph Node Response Rate [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Time to Response [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Progression-Free Survival [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause.

  • Change in Health-related Quality of Life [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]

    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.


  • Change in Karnofsky Performance Status [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    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.

  • Study Drug Exposure [ Time Frame: From enrollment until all subjects completed ≥ 24 weeks of evaluation (up to 24 months) ] [ Designated as safety issue: No ]
    The average idelalisib exposure was summarized.

  • Idelalisib Plasma Concentration [ Time Frame: Predose and at 1.5 hours (± 5 minutes) postdose on Day 29 ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) Parameter: Cmax [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29 ] [ Designated as safety issue: No ]
    Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.

  • Pharmacokinetic (PK) Parameter: Tmax [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29 ] [ Designated as safety issue: No ]
    Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).

  • Pharmacokinetic (PK) Parameter: AUClast [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29 ] [ Designated as safety issue: No ]
    AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration


Enrollment: 125
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Karnofsky performance score 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
    • 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

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. Patients 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 patient, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01282424

  Show 55 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Wayne Godfrey, MD Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01282424     History of Changes
Other Study ID Numbers: 101-09, 2010-022155-33
Study First Received: January 21, 2011
Results First Received: August 22, 2014
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
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)

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, B-Cell
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 29, 2014