Dose Optimization Study of Idelalisib in Follicular Lymphoma

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Follicular Lymphoma

Treatments: Drug: Idelalisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02536300

2015-000366-66 (EudraCT Number)

GS-US-313-1580

Details and patient eligibility

About

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.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 World Health Organization (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 available therapeutic options. Note: Rituximab maintenance is not routinely considered a separate line of therapy when it is given as part of the prior rituximab-containing regimen given over a number of cycles followed by maintenance. Rituximab monotherapy may be considered a separate line of therapy when disease relapse occurs between the initiation of rituximab monotherapy and the preceding line of therapy. If there are any ambiguities about eligibility, the site should consult with the medical monitor.
• 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 specifically CMV antiviral prophylaxis within 28 days prior to the screening visits CMV test

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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96 participants in 3 patient groups

Idelalisib 150 mg BID

Experimental group

Description:

Participants 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.

Treatment:

Drug: Idelalisib

Idelalisib 100 mg BID

Experimental group

Description:

Participants 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.

Treatment:

Drug: Idelalisib

Idelalisib 150 mg BID INT

Experimental group

Description:

Participants will receive idelalisib 150 mg twice daily in 28-day cycles with 21 days on-treatment and 7 days off-treatment.

Treatment:

Drug: Idelalisib