Clinical Trials /

Dose Optimization Study of Idelalisib in Follicular Lymphoma

NCT02536300

Description:

The primary objective of this study is to establish a safe and effective dosing regimen of idelalisib in participants with relapsed or refractory follicular lymphoma (FL) who have no other therapeutic options.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Dose Optimization Study of Idelalisib in Follicular Lymphoma
  • Official Title: Dose Optimization Study of Idelalisib in Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GS-US-313-1580
  • SECONDARY ID: 2015-000366-66
  • NCT ID: NCT02536300

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
IdelalisibZydelig®, GS-1101, CAL-101Idelalisib 150 mg Continuously

Purpose

The primary objective of this study is to establish a safe and effective dosing regimen of idelalisib in participants with relapsed or refractory follicular lymphoma (FL) who have no other therapeutic options.

Trial Arms

NameTypeDescriptionInterventions
Idelalisib 150 mg ContinuouslyExperimentalParticipants will receive idelalisib 150 mg twice daily continuously. For participants enrolled prior to protocol amendment 5: Based on the independent review committee (IRC) response assessment, participants may be discontinued from the study or may receive blinded or open-label idelalisib 150 mg twice daily.
  • Idelalisib
Idelalisib 100 mgExperimentalParticipants will receive idelalisib 100 mg twice daily continuously. Based on the IRC response assessment, participants may either be dose escalated to open-label 150 mg twice daily or maintain blind and continue on idelalisib 100 mg twice daily. As of protocol amendment 5, enrollment to this arm has been closed.
  • Idelalisib
Idelalisib 150 mg 28-Day CyclesExperimentalParticipants will receive idelalisib 150 mg twice daily in 28-day cycles with 21 days on-treatment and 7 days off-treatment.
  • Idelalisib

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically confirmed diagnosis of B-cell follicular lymphoma (FL), and grade
             limited to 1, 2, or 3a based on criteria established by the WHO 2008 classification of
             tumors of hematopoietic and lymphoid tissues

          -  Relapsed or refractory FL and have received at least 2 lines of prior therapy for FL
             and have no other therapeutic options

          -  Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease per Lugano Classification
             Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined
             as the presence of ≥ 1 lesion that measures ≥ 1.5 cm in the longest dimension (LD) and
             ≥ 1.0 cm in the longest perpendicular dimension (LPD) as assessed by positron emission
             tomography-computed tomography (PET-CT), computed tomography (CT) or magnetic
             resonance imaging (MRI)

          -  Required baseline central laboratory data in protocol.

          -  For female individuals of childbearing potential and male individuals of reproductive
             potential, willingness to use a protocol- recommended method of contraception

          -  Lactating females must agree to discontinue nursing

          -  Willing and able to comply with scheduled visits, drug administration plan, imaging
             studies, laboratory tests, other study procedures, and study restrictions including
             mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP)

        Key Exclusion Criteria:

          -  History of lymphoid malignancy other than FL (eg, diffuse large B-cell lymphoma)

          -  Known history of, or clinically apparent, central nervous system (CNS) lymphoma or
             leptomeningeal lymphoma.

          -  Known presence of intermediate- or high-grade myelodysplastic syndrome.

          -  Known history of serious allergic reaction including anaphylaxis or Stevens- Johnson
             syndrome/ toxic epidermal necrolysis

          -  History of a non-lymphoid malignancy except for protocol allowed exceptions

          -  Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
             enrollment

          -  Known history of drug-induced liver injury, chronic active hepatitis B virus (HBV),
             chronic active hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic
             steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary
             cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasis

          -  History of or ongoing drug-induced pneumonitis

          -  History of or ongoing inflammatory bowel disease

          -  Known human immunodeficiency virus (HIV) infection

          -  History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

          -  Ongoing immunosuppressive therapy, including systemic corticosteroids (> 10 mg
             prednisone or equivalent/day) with the exception of the use of topical, enteric, or
             inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for
             autoimmune anemia and/or thrombocytopenia

          -  Concurrent participation in another therapeutic clinical trial

          -  Prior treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors

          -  Cytomegalovirus (CMV)- Ongoing infection, treatment, or prophylaxis within 28 days
             prior to the Screening Visit CMV test

        Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to end of radiographic assessment (approximately Week 84)
Safety Issue:
Description:ORR is defined as the proportion of participants who achieve a partial response (PR) or complete response (CR).

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to end of radiographic assessment (approximately Week 84)
Safety Issue:
Description:DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression by IRC or death from any cause.
Measure:Overall Response Rate by Week 24
Time Frame:Up to Week 24
Safety Issue:
Description:ORR by Week 24 is defined as the proportion of participants who achieve a PR or CR by Week 24.
Measure:Overall Safety Profile of Idelalisib
Time Frame:Up to end of study (approximately 10 years)
Safety Issue:
Description:The overall safety profile of idelalisib will include the incidence of adverse events (AE), clinically significant laboratory abnormalities, ≥ Grade 3 AEs, idelalisib-related AEs, serious adverse events (SAEs), and AEs leading to interruption, reduction, or discontinuation of idelalisib.
Measure:Time to onset of adverse events of interest (AEI)
Time Frame:Up to end of study (approximately 10 years)
Safety Issue:
Description:Time to onset of AEI is defined as the interval from the start of idelalisib treatment to the first documentation of start of AEI.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to end of radiographic assessment (approximately Week 84)
Safety Issue:
Description:PFS is defined as the interval from randomization to the earlier of the first documentation of disease progression by IRC or death from any cause.
Measure:Overall Survival (OS)
Time Frame:Up to end of study (approximately 10 years)
Safety Issue:
Description:OS is defined as the interval from randomization to death from any cause.
Measure:Idelalisib Trough (pre-dose) and Peak (1.5-hour samples) Plasma Concentrations
Time Frame:Predose and 1.5 hours postdose in the morning up to Week 48
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

December 13, 2019