Dose Optimization Study of Idelalisib in Follicular Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 96
- 试验地点
- 66
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Double-blind: Prior to protocol amendment 5; Open-label: Participants enrolled as of protocol amendment 5
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Idelalisib 150 mg BID
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.
干预措施: Idelalisib (Drug)
Idelalisib 100 mg BID
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.
干预措施: Idelalisib (Drug)
Idelalisib 150 mg BID INT
Participants will receive idelalisib 150 mg twice daily in 28-day cycles with 21 days on-treatment and 7 days off-treatment.
干预措施: Idelalisib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Randomization up to end of treatment (maximum duration: 73.5 months)
ORR was defined as percentage of participants who achieve a partial response (PR) or complete response (CR). PR criteria: No evidence of new disease, a ≥50% decrease from baseline in sum of products of diameters (SPD) of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. Persistence of bone marrow involvement in a participant who meets other criteria for CR based on the disappearance of all nodal and extra-nodal masses. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (≤1.5 cm in longest dimension (LD) for large nodes and ≤1.0 cm in LD, ≤1.0 cm in longest perpendicular dimension (LPD) for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow.
Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs)
时间窗: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.
次要结局
- Duration of Response (DOR)(From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months))
- Overall Response Rate (ORR) by Week 24(First dose date up to Week 24)
- Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib(First dose date up to 30 days after last dose of study drug (maximum 64.6 months))
- Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities(First dose date up to 30 days after last dose of study drug (maximum 64.6 months))
- Time to Onset of Adverse Events of Interest (AEIs)(First dose date up to 30 days after last dose of study drug (maximum 64.6 months))
- Progression-Free Survival (PFS)(Randomization up to PD or death from any cause (maximum duration: 73.5 months))
- Overall Survival (OS)(Randomization up to death from any cause (maximum duration: 73.5 months))
- Trough Plasma Concentration of Idelalisib(Predose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48)
- Peak Plasma Concentration of Idelalisib(1.5 hours postdose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48)