TREND-FL: Tafasitamab and Rituximab to Enhance Outcomes in Patients With Newly Diagnosed Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Complete remission at the best response
研究概览
简要总结
This phase II trial tests how well tafasitamab and rituximab works for the treatment of newly diagnosed follicular lymphoma. Tafasitamab is a monoclonal antibody. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving tadasitamab and rituximab may work well to treat patients with newly diagnosed follicular lymphoma.
详细描述
OUTLINE:
CYCLES 1-3: Patients receive rituximab intravenously (IV) on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥ 18 years old
- •Patients must have histologic confirmation of follicular lymphoma (FL) (grade 1, 2, and 3A or classic follicular lymphoma)
- •Meeting any one of the following criteria for therapy initiation:
- •Involvement of ≥ 3 nodal sites, each with diameter of ≥ 3 cm.
- •Any nodal or extranodal tumor mass with a diameter of ≥ 7 cm.
- •B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months) attributed to FL.
- •Risk of local compressive symptoms that may result in organ compromise.
- •Splenomegaly with the inferior margin below the umbilical line or splenic lesion without splenomegaly.
- •Significant cytopenia (absolute neutrophil count < 1500/mm3, platelets < 100,000/uL, hemoglobin < 10 g/dL)
- •Leukemia (> 5,0000/uL circulating lymphocytes)
- •Pleural effusion or ascites attributed to lymphoma
- •Have measurable nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on CT or fludeoxyglucose (FDG)-PET, or a FDG-avid extranodal measurable site measuring at least 1.0 cm in longest dimension. Measurable disease also includes spleen size more than 13 cm in vertical length
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Absolute neutrophil count ≥ 1500/mm^3 (unless due to lymphoma involvement of the bone marrow or spleen)
- •Platelets ≥ 75,000/mm^3 (unless due to bone marrow involvement by lymphoma)
- •Hemoglobin ≥ 8 g/dL (unless due to bone marrow involvement by lymphoma)
- •Total bilirubin ≤ 2.0 mg/dL, except for patients with documented lymphoma involvement of liver or with a known history of Gilbert's disease
- •Alkaline phosphatase/aspartate aminotransferase (AST)/(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 3 × institutional upper limit of normal, except for patients with documented liver involvement
- •Creatinine clearance ≥ 30 ml/min
- •Fertile male and women of child bearing potential (WOCBP) patients must be willing to use highly effective contraceptive methods from study recruitment to at least 6 months after the last dose of study treatment
- •Ability to understand and willingness to sign a written informed consent document
排除标准
- •FL grade 3B or transformed FL
- •Patients receiving any other investigational agents
- •Patients with known central nervous system involvement of lymphoma
- •History of a second primary malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. Malignancies treated curatively or at low-risk of progressing at the judgment of the primary investigator (PI) may be included
- •Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection at study enrollment
- •Uncontrolled intercurrent illness such as: history of myocardial infarction (MI) in the last 6 months, congestive heart failure New York Heart Association (NYHA) Class III-IV, uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (> 10 mg daily prednisone equivalent)
- •Prior use of any monoclonal antibody within 4 weeks before the first administration
- •Breastfeeding or pregnant women
- •Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody are eligible if the corresponding polymerase chain reaction (PCR) test is negative prior to enrollment. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis as per institutional guidelines
- •History of human immunodeficiency virus (HIV) infection uncles the viral load is undetectable and CD4 count is at least 400
- •History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- •Major surgery (excluding lymph node biopsy) within 28 days prior to signing the informed consent form (ICF) unless the participant is recovered at the time of signing the ICF
- •Any systemic anti-lymphoma and/or investigational therapy within 28 days prior to the start of cycle 1
- •Administration of a live vaccine within 28 days prior to the start of study treatment (cycle 1 day 1)
- •History of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, immunomodulatory drugs, rituximab, other monocolonal antibodies (mAbs), and/or the excipients contained in the study drug formulations
研究组 & 干预措施
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Rituximab (Biological)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Survey Administration (Other)
Treatment (Tafasitamab and rituximab)
CYCLES 1-3: Patients receive rituximab IV on day 1 and tafasitamab IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CYCLES 4-6; Patients receive rituximab IV on day 1 and tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients then undergo disease assessment. Patients with complete response undergo active surveillance. Patients with less than complete response go on to receive cycles 7-12.
CYCLES 7-12: Patients receive tafasitamab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo PET scan, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Tafasitamab (Biological)
结局指标
主要结局
Complete remission at the best response
时间窗: Up to 1 year of starting treatment
Assessed by positron emission tomography (PET)/computed tomography (CT) and diagnostic CT scans based on Lugano criteria. Will report the number of complete response (CR) at the best response within one year of starting study treatment and the estimated CR rate with 95% exact binomial confidence interval (CI).
次要结局
- Incidence of adverse events (AEs)(Up to 30 days after completing the last dose of study treatment)
- Overall response at the best response(Up to 1 year of starting treatment)
- Complete remission(After cycle 6 (cycle length =28 days))
- Progression free survival (PFS)(From cycle 1 day 1 to disease progression or death, up to 5 years)
- Overall survival (OS)(From cycle 1 day 1 to death regardless of the causes of death, up to 5 years)
- Duration of response(From first partial response or complete response to progression of disease or death, up to 5 years)