Phase 2 Single-Arm, Open-Label Study of Nivolumab in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Response Rate for Participants Who Achieve a CR or PR [CT-based Response]
研究概览
简要总结
This phase II trial studies how well nivolumab works in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the clinical benefit of nivolumab in T-cell lymphomas, as measured by objective response rate (ORR) within 12 cycles according to the Lugano Classification Response Criteria (2014).
SECONDARY OBJECTIVES:
I. To assess safety and tolerability of the regimen in this patient population. II. To assess progression-free survival (PFS). III. To assess duration of response (DOR). IV. To assess overall survival (OS).
TERTIARY OBJECTIVES:
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
- •Relapsed or refractory T-cell lymphoma (TCL) biopsy-proven =< 6 months prior to registration, including the following subtypes:
- •Peripheral T-cell lymphoma, not otherwise specified
- •Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) negative, primary systemic type
- •Angioimmunoblastic T-cell lymphoma
- •Extranodal natural killer (NK)/T-cell lymphoma, nasal type
- •Adult T-cell lymphoma/leukemia (human T-lymphotropic virus 1 [HTLV1]+)
- •Blastic NK-cell lymphoma
- •Enteropathy-associated T-cell lymphoma
- •Hepatosplenic gamma delta T-cell lymphoma
- •Transformed mycosis fungoides
- •T/NK-cell lymphoma, unclassifiable
- •Measurable disease: subjects must have at least one lesion that is > 15mm (1.5 cm) in the longest diameter on cross-sectional imaging and measureable in two perpendicular dimensions per computed tomography (spiral CT) or magnetic resonance imaging (MRI)
- •After failure of allogeneic stem cell transplant (ASCT) or after failure of frontline therapy in subjects who declined or are not ASCT candidates
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •White blood cell (WBC) >= 3000/mm^3
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin > 9.0 g/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation due to Gilbert's Syndrome
- •Aspartate transaminase (AST) =< 2.5 x ULN
- •Creatinine =< 2.0 mg/dL
- •Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula
- •Negative serum or urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only Note: Persons of child-bearing potential (POCBP) must use appropriate method(s) of contraception; POCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug; men who are sexually active with POCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with POCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; persons who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception; should a person become pregnant or suspect being pregnant while participating in this study, the person should inform the treating physician immediately
- •Provide written informed consent
- •Willing to return to enrolling institution for follow-up during the Active Monitoring phase of the study
- •Willing to provide tissue and blood samples for correlative research purposes
排除标准
- •All primary cutaneous T-cell lymphomas
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Active, known or suspected autoimmune disease Note: subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment
- •Use of systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications < 14 days of registration Note: inhaled or topical steroids are permitted; > 10 mg daily prednisone equivalents are permitted only in adrenal insufficiency in the absence of active autoimmune disease
- •Prohibited treatments and or therapies
- •Autologous stem cell transplant (ASCT) =< 12 weeks prior to first dose of the study drug
- •Prior treatments (window prior to registration):
- •Chemotherapy =< 2 weeks
- •Nitrosureas =< 6 weeks
- •Therapeutic anticancer antibodies =< 4 weeks
- •Radio- or toxin immunoconjugates =< 10 weeks
- •Radiation therapy =< 3 weeks
- •Or major surgery =< 2 weeks
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
- •Prior allogeneic stem cell transplant (SCT)
- •Chest radiation =< 24 weeks prior to registration
- •Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, active hepatitis B virus surface antigen (HBV sAg+), active hepatitis C (if Ab+ then PCR+) indicating acute or chronic infection
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Other active malignancy =< 3 years prior to registration EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
- •Active central nervous system (CNS) involvement or leptomeningeal involvement
- •History of pancreatitis
研究组 & 干预措施
Treatment (nivolumab)
Patients receive nivolumab IV over 60 minutes on day 1. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, complete response, or partial response receive nivolumab IV over 60 minutes on day 1 of course 9. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (nivolumab)
Patients receive nivolumab IV over 60 minutes on day 1. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, complete response, or partial response receive nivolumab IV over 60 minutes on day 1 of course 9. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Response Rate for Participants Who Achieve a CR or PR [CT-based Response]
时间窗: Up to 390 days
The response rate for participants who achieve a CR or PR is defined as the percentage of participants who achieve a CR or PR assessed according to the revised Lugano Classification Response criteria. Complete response (CR): target nodes/nodal masses must regress to \<=1.5 cm in longest transverse diameter (LDi). Partial response (PR): \>= 50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites.
次要结局
- Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events(Up to 390 days)
- Response Rate for Participants Who Achieve a CMR or PMR [PET-CT-based Response](Up to 390 days)
- Duration of Response (DOR)(Up to 390 days)
- Progression-Free Survival (PFS)(The time from registration to relapse or death due to any cause, an average of 2 years)
- Overall Survival (OS)(The time from registration to death due to any cause, assessed up to 2 years)