Phase I Study Utilizing Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor Nivolumab for Relapsed/Refractory Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence of Product-Emergent Adverse Events
研究概览
简要总结
This is a Phase I, open-label multi-site trial designed to evaluate the safety of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B).
The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.
详细描述
This Phase I, open-label multi-site trial is designed to evaluate the safety of administering rapidly-generated multi-antigen-specific T lymphocytes with the PD1 inhibitor Nivolumab, to relapsed/refractory (rel/ref) lymphoma patients with measurable disease (group A) or as adjunctive therapy following autologous HSCT (group B).
This study will first enroll 6 patients total (in Groups A and B) in the initial safety monitoring or DLT group prior to the expansion phase where additional 12 patients (6 in Group A and 6 in Group B) will be enrolled. TAA-T cells will be generated from patient's lymphocytes obtained from patient's PBMC.
If patient meets eligibility criteria for TAA-T cell infusion, the patient (Group A or Group B) will receive two TAA-T cell infusions given 2 weeks apart, where the expected volume of infusion is 1 to 10 cc.
Both TAA-T cells and Nivolumab will be given at the doses below with allowed de-escalation of both doses as follows:
- TAA-T cell dose: 2 x 107 cells/m2 per infusion
- Nivolumab: For patients <18 years, 3 mg/kg/dose (maximum 240mg/dose) every 2 weeks. For adult patients ≥18 years, a dose of 240mg every 2 weeks or 480mg every 4 weeks
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
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease Specific Inclusion Criteria
- •Group A (patients with measurable disease) Relapsed/Refractory Hodgkin Lymphoma (HL) and Diffuse Large B cell Lymphoma (DLBCL) DLBCL
- •* Patients who have failed at least 2 lines of prior therapy with a failed attempt at both an autologous stem cell transplant and chimeric antigen receptor T cell therapy.
- •* Patients who are deemed autologous stem cell transplant ineligible and have failed only one line of prior therapy.
- •* Systemic therapies to treat prior indolent lymphomas count towards previous DLBCL lines of therapy unless the treatment was anti-CD20 antibody monotherapy.
- •* Rel/ref HL failing more than or equal to 1 salvage regimens, including prior Brentuximab Vedotin (BV)
- •* Rel/ref after autologous HSCT
- •Group B (consolidation after auto-HSCT for patients at high risk for relapse) DLBCL
- •* Patients with \< CMR/CR (by PET/CT) with initial treatment regimen
- •* Patients with relapse \<12 months from diagnosis or \<6 months from completion of initial therapy
- •* Patients with \1 salvage regimen prior to autologous HSCT HL
- •* Patients with relapse \<12 months from diagnosis or \<6 months from completion of initial therapy
- •* Patients with \1 salvage regimen prior to autologous HSCT
- •Recipient Inclusion Criteria for Initial and Subsequent Procurements (TAA-T Cell Generation):
- •* Age \>12 years
- •* Karnofsky/Lansky score of more than or equal to 50 (see appendix C).
- •* ALC \> 600
- •* Patients receiving Granulocyte colony-stimulating factor (G-CSF) are recommended a washout period of a minimum of two weeks before procurement
- •* Agree to use contraceptive measures during study protocol participation (when age appropriate)
- •* Patient or parent/guardian capable of providing informed consent
排除标准
- •for Initial and Subsequent Procurements (TAA-T Cell Generation):
- •Prior allogeneic BMT
- •Prior solid organ transplant
- •Patient who has received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment
- •Patient with uncontrolled infections
- •Patient with active HIV
- •Pregnancy or lactating
- •Failure to meet institutional guidelines for treatment with Nivolumab
- •Recipient Inclusion Criteria for Initial and Subsequent TAA-T Cell Infusions:
- •Age >12 years
- •Patient has received at least 8 weeks of Nivolumab
- •Patients with Grade 1 toxicities attributed to Nivolumab will be eligible at the discretion of the PI. Toxicities include but not limited to: laboratory abnormalities in thyroid function tests suggestive of hypothyroidism, thyroiditis or thyroid dysfunction adequately managed with thyroid hormone replacement, or abnormalities in amylase, lipase
- •Steroids less than 0.5 mg/kg/day prednisone or equivalent
- •Karnofsky/Lansky score of more than or equal to 50
- •Pulse oximetry of > 90% on room air
- •Bilirubin less than or equal to 2.5 mg/dL, AST/ALT less than or equal to 5x upper limit of normal, serum creatinine < 1.0 or 2x the upper limit of normal (whichever is higher)
- •Absolute neutrophil count > 250/µL (may be supported with GCSF)
- •Agree to use contraceptive measures during study protocol participation (when age appropriate)
- •Patient or parent/guardian capable of providing informed consent
- •Recipient Exclusion Criteria for Initial and Subsequent TAA-T Cell Infusions:
- •Investigational therapies within 28 days prior to screening for enrollment
- •Uncontrolled infections
- •Patient with ≥ grade 1 or symptomatic non-hematologic toxicities from prior therapies
研究组 & 干预措施
Nivolumab with TAA-T cell
Patients will receive doses of Nivolumab at a minimum of 8 weeks prior to first TAA-T cell infusion and additional dose(s) of Nivolumab will be given after 4 weeks following second TAA-T cell infusion starting at week 7 from first infusion of TAA-T.If patient meets eligibility criteria for TAA-T cell infusion, the patient will receive two TAA-T cell infusions given 2 weeks apart
干预措施: TAA-T cells (Biological)
Nivolumab with TAA-T cell
Patients will receive doses of Nivolumab at a minimum of 8 weeks prior to first TAA-T cell infusion and additional dose(s) of Nivolumab will be given after 4 weeks following second TAA-T cell infusion starting at week 7 from first infusion of TAA-T.If patient meets eligibility criteria for TAA-T cell infusion, the patient will receive two TAA-T cell infusions given 2 weeks apart
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of Product-Emergent Adverse Events
时间窗: 6 weeks from the first TAA-T cell administrations
Number of participants with grades 3-5 infusion-related and grades 4-5 non-hematological adverse events that are not due to the original malignancy, or pre-existing co-morbidities at least 6 weeks of the first dose of TAA-T infusion as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03, change from baseline up to week 6.
次要结局
- Tumor response to combination immunotherapy(1 year)
研究者
Catherine Bollard
Director - Center for Cancer and Immunology Research
Children's National Research Institute