A Phase 1/2 Study of N-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 43
- 试验地点
- 8
- 主要终点
- Overall Response Rate
研究概览
简要总结
This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of N-803 in patients with relapse/refractory indolent B cell non-Hodgkin lymphoma in conjunction with rituximab.
详细描述
The purpose of this study is to evaluate the safety and tolerability, identify the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and designate a dose level for Phase 2. Also characterize the immunogenicity, pharmacokinetic profile, and biomarker serum levels of N-803 in treated patients.
The effect of N-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number, phenotype and repertoire of peripheral blood T (total and subsets) and NK cells will be evaluated. In addition, a subset of patients will be evaluated for changes in lymph node immune composition. Anti-tumor responses and survival data will also be collected in this trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed diagnosis of iNHL (Follicular lymphoma grade 1, 2, 3a; marginal zone lymphoma; small lymphocytic lymphoma or lymphoplasmacytic lymphoma) after treatment with at least 1 or more prior rituximab-containing regimens.
- •Anti-CD20 mAb-refractory disease is defined as progressive disease while on rituximab (or another treatment of an anti-CD20 monoclonal antibody) or progression within 6 months of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
- •Anti-CD20 mAb-sensitive disease is defined by a response to a prior rituximab-containing (or another treatment of an anti-CD20 monoclonal antibody) regimen, and relapse more than 6 months from the last administration of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
- •Measurable disease:
- •At least one lymph node group ≥ 1.5 cm in longest transverse dimension. Patients with cutaneous only disease may be enrolled if they have a clearly measurable skin lesion.
- •Relapsed or Refractory iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment of an anti-CD20 antibody-containing) regimens for lymphoma
- •PRIOR/CONCURRENT THERAPY:
- •No anti-lymphoma treatments within 28 days before the start of study treatment.
- •Must have recovered from side effects of prior treatments.
- •PATIENT CHARACTERISTICS:
- •Performance Status
- •ECOG 0, 1, or 2
- •Renal Function • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ≤ 1.5 X ULN
- •Bone Marrow Reserve
- •Platelets ≥30,000/uL
- •Hemoglobin ≥ 8g/dL
- •Absolute Lymphocytes ≥800/uL
- •ANC/AGC ≥750/uL
- •Hepatic Function
- •Total bilirubin ≤ 2.0 X ULN (unless Gilbert's Syndrome or disease infiltration of liver is present)
- •AST, ALT ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver lymphoma is present)
- •No positive Hep C serology or active Hep B infection
- •Cardiovascular
- •No congestive heart failure < 6 months
- •No unstable angina pectoris < 6 months
- •No myocardial infarction < 6 months
- •No history of ventricular arrhythmias or severe cardiac dysfunction
- •No history of uncontrollable supraventricular arrhythmias
- •No NYHA Class > II CHF
- •No marked baseline prolongation of QT/QTc interval
- •Normal clinical assessment of pulmonary function
- •Negative serum pregnancy test if female and of childbearing potential
- •Women who are not pregnant or nursing
- •Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
- •No known autoimmune disease other than corrected hypothyroidism
- •No known prior organ allograft or allogeneic transplantation
- •Not HIV positive
- •No active CNS involvement with lymphoma
- •No psychiatric illness/social situation that would limit compliance
- •No other illness that in the opinion of the investigator would exclude the subject from participating in the study
- •Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
- •No active systemic infection requiring parenteral antibiotic therapy
- •No disease requiring systemic immunosuppressive therapy (inhaled or topical steroids are allowed). Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
- •No known histologic transformation from iNHL to DLBCL
排除标准
- 未提供
结局指标
主要结局
Overall Response Rate
时间窗: 60 months
For Phase 1 and 2, overall response rate (ORR) will be calculated as the ratio of the number of patients who demonstrated response (CR+PR) divided by the number of patients in the Evaluable population. Response and disease progression criteria were defined by the 2007 IHP response assessments for malignant lymphoma.
MTD or MED of N-803: IV 1, 3, 6 μg/kg, SQ 6, 10, 15, 20 μg/kg
时间窗: 9 months
Maximum Tolerated Dose level (MTD) is defined as a dose level at which \<2 out of 6 patients experienced Dose Limiting Toxicity (DLT) and that is one level below a dose that was not tolerated. Minimal Efficacious Dose (MED) is defined as a dose level which produces an Absolute Lymphocyte Count (ALC) ≥25,000/μL sustained for 14 days or a total WBC ≥35,000/μL sustained for 14 days among 2/3 or 4/6 of patients. The elevated ALC cannot be attributed to circulating lymphoma cells. Dose levels for N-803 1, 3, 6 μg/kg IV, and 6, 10, 15, 20 μg/kg subcutaneous (SQ) were used to determine the MTD or MED.
Number of Participants With Treatment Emergent Adverse Events
时间窗: 30 days after last dose, up to 40 weeks
Treatment Emergent Adverse Event is defined as any AE that begins or worsens in grade after the start of study treatment until 30 days after the last dose of study treatment or end of study period, whichever is later.
次要结局
未报告次要终点