A Phase II Study of Acalabrutinib, Lenalidomide, and Rituximab (aR2) in Patients With Previously Untreated Follicular Lymphoma
概览
- 阶段
- 2 期
- 干预措施
- Acalabrutinib
- 疾病 / 适应症
- Ann Arbor Stage III Grade 1 Follicular Lymphoma
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Complete remission rate
- 状态
- 进行中（未招募）
- 最后更新
- 16天前
概览
简要总结
This phase II trial studies how well acalabrutinib, lenalidomide, and rituximab work in treating patients with CD20 positive stage III-IV, grade 1-3a follicular lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib, lenalidomide, and rituximab may help to control the disease.
详细描述
PRIMARY OBJECTIVE: I. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) (determined by complete remission \[CR\] rate by the end of treatment). SECONDARY OBJECTIVES: I. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by objective response rate (ORR) at the end of treatment, duration of response (DOR), progression rate within 24 months from treatment initiation (progression-free survival \[PFS\] 24), PFS and overall survival (OS). II. To evaluate the safety and tolerability of acalabrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL. EXPLORATORY OBJECTIVE: I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance of the 3-drug combination. OUTLINE: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Beginning cycle 2, patients receive lenalidomide PO once daily (QD) on days 1-21 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
研究者
入排标准
入选标准
- •Histologically confirmed CD20 positive (+) follicular lymphoma, grade 1, 2, or 3a
- •Have had no prior systemic treatment for lymphoma
- •Bi-dimensionally measurable disease, with at least one mass lesion \>= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
- •Meeting Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria for initiation of treatment
- •Stage III or IV disease
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Absolute neutrophil count (ANC) \>= 1,000/mm\^3, independent of growth factor support (within 28 days prior to signing informed consent)
- •Platelet counts \>= 100,000/mm\^3 or \>= 50,000/mm\^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent)
- •Hemoglobin \> 8 g/dL, independent of transfusion support (within 28 days prior to signing informed consent)
- •Serum aspartate transaminase (AST) or alanine transaminase (ALT) \< 2 x upper limit of normal (ULN) (within 28 days prior to signing informed consent)
排除标准
- •Known active central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission \> 6 months
- •Evidence of diffuse large B-cell transformation
- •Grade 3b FL
- •Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for \>= 5 years and felt to be at low risk for recurrence by the treating physician, except:
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated cervical carcinoma in situ without evidence of disease
- •Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib or lenalidomide capsules, or put the study outcomes at undue risk
- •Known history of human immunodeficiency virus (HIV), or active hepatitis C Virus, or active hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed John Cunningham (JC) virus infection
- •Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative
- •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of \> 10 mg/day of prednisone) within 28 days of the first dose of study drug
研究组 & 干预措施
Treatment (acalabrutinib, lenalidomide, rituximab)
Patients receive acalabrutinib PO BID on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21 and rituximab IV on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Acalabrutinib
Treatment (acalabrutinib, lenalidomide, rituximab)
Patients receive acalabrutinib PO BID on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21 and rituximab IV on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide
Treatment (acalabrutinib, lenalidomide, rituximab)
Patients receive acalabrutinib PO BID on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21 and rituximab IV on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab
结局指标
主要结局
Complete remission rate
时间窗: (Up to end of treatment; 1 year)
Will be based on Cheson, Lugano classification 2014. The number and percentage of subjects with a complete remission at the end of treatment will be tabulated.
次要结局
- Duration of response(From the time by which measurement criteria for complete response or partial response, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 3 years)
- Overall response rate (complete response + partial response)((At the end of treatment ; 1 year ))
- Progression-free survival within 24 months from treatment initiation(From the treatment start date (cycle 1, day 1) until the firstdate of objectively documented progressive disease or date of death from any cause, assessed up to 24 months)
- Progression-free survival(From the date of cycle 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death, assessed up to 3 years)
- Overall survival(From the date of cycle 1, day 1 to the date of death regardless of cause, assessed up to 3 years)
- Frequency, severity, and relatedness of treatment-emergent adverse events (AEs)(Up to 3 years)
- Frequency of treatment-emergent AEs requiring study drug discontinuation or dose reduction(Up to 3 years)