A Phase 3, Randomized, Double-blind Study of Duvelisib Administered in Combination With Rituximab and Bendamustine vs Placebo Administered in Combination With Rituximab and Bendamustine in Subjects With Previously-Treated Indolent Non-Hodgkin Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study will evaluate the efficacy and safety of duvelisib in combination with bendamustine and rituximab (DBR) vs placebo in combination with bendamustine and rituximab (PBR) in subjects with previously-treated indolent non-Hodgkin lymphoma (iNHL).
详细描述
Study IPI-145-22 is an international, multicenter, randomized, double-blind, placebo-controlled, two-arm Phase 3 study designed to evaluate efficacy and safety of DBR vs PBR in subjects with previously-treated iNHL (including follicular lymphoma [FL], small lymphocytic lymphoma [SLL] and marginal zone lymphoma [MZL]).
Approximately 600 subjects will receive 25 mg of duvelisib or placebo, orally BID for 28 day continuous cycles, in combination with 375 mg/m2 of rituximab given on Day 1 of Cycles 1-6 and 90 mg/m2 of bendamustine given on Day 1 and Day 2 of Cycles 1-6. Subjects will receive duvelisib until disease progression or unacceptable toxicity.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of iNHL with one of the following histologic sub-types and grade:
- •Follicular lymphoma (FL)Grade 1, 2, or 3a
- •Small lymphocytic lymphoma (SLL)
- •Marginal zone lymphoma (MZL)( splenic, nodal, or extranodal)
- •Have received the following systemic treatments for iNHL:
- •an anti-CD20 antibody; and
- •chemotherapy
- •At least 1 measurable disease lesion > 1.5 cm in at least one dimension by computed tomography (CT)/CT-PET or magnetic resonance imaging (MRI)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (corresponds to Karnofsky Performance Status [(KPS) ≥60%])
排除标准
- •Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
- •Refractory to bendamustine + rituximab therapy or single-agent bendamustine 120 mg/m2, with refractory defined as:
- •Progression of disease while receiving or within 6 months of completing treatment
- •Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs
- •Received prior allogeneic transplant
- •Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
- •Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- •History of tuberculosis treatment within the two years prior to randomization
- •History of chronic liver disease, veno-occlusive disease, or alcohol abuse
- •Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) daily (QD)
- •Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
- •Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
- •Concurrent active malignancy other than adequately treated non-melanoma skin cancer or lentigo maligna without evidence of invasive disease or adequately treated cervical carcinoma in situ without evidence of disease
- •History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening
- •History of progressive multifocal leukoencephalopathy
研究组 & 干预措施
Duvelisib + Rituximab + Bendamustine
Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.
Bendamustine is administered as an intravenous (IV) infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Duvelisib (Drug)
Duvelisib + Rituximab + Bendamustine
Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.
Bendamustine is administered as an intravenous (IV) infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Rituximab (Drug)
Duvelisib + Rituximab + Bendamustine
Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.
Bendamustine is administered as an intravenous (IV) infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Bendamustine (Drug)
Placebo + Rituximab + Bendamustine
Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules of duvelisib.
Bendamustine is administered as an IV infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Placebo (Drug)
Placebo + Rituximab + Bendamustine
Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules of duvelisib.
Bendamustine is administered as an IV infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Rituximab (Drug)
Placebo + Rituximab + Bendamustine
Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules of duvelisib.
Bendamustine is administered as an IV infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg.
Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
干预措施: Bendamustine (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From date of enrollment until the date of first documentation of progression or date of death from any cause, whatever came first, assessed up to 78 months
次要结局
- Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)(Continuous from informed consent until 30 days from last dose)
- Pharmacokinetics (PK)(Cycle 1 and Cycle 2 (each cycle is 28 days))
- Complete Response (CRR)(Every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.)
- Overall Response Rate (ORR)(Every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.)
- Overall Survival (OS)(Every 6 months for up to 5 years from date of randomization)
- Duration of Response (DOR)(Every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.)