A Pilot Study of Atezolizumab (MPDL3280A) Following Adoptive Cell Transfer in Active Hematologic or Solid Tumor Malignancies
概览
- 阶段
- 1 期
- 干预措施
- Laboratory Biomarker Analysis
- 疾病 / 适应症
- Hematopoietic and Lymphoid Cell Neoplasm
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 40
- 试验地点
- 18
- 主要终点
- Incidence of adverse events
- 状态
- 进行中（未招募）
- 最后更新
- 11天前
概览
简要总结
This pilot phase I trial studies the side effects of atezolizumab in treating patients with cancer following adoptive cell transfer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVE: I. To evaluate the safety of atezolizumab (MPDL3280A) administration in patients who have received adoptive cell transfer (ACT) prior to enrollment. SECONDARY OBJECTIVES: I. To evaluate the expansion of engrafted T cells following atezolizumab administration in the peripheral blood and within the tumor microenvironment. II. To evaluate the phenotype and function of engrafted T cells following atezolizumab administration. III. To observe and record anti-tumor activity. IV. To evaluate the response rate using immune related Response Criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, or other tumor-specific criteria. V. To evaluate survival outcomes and progression free survival using irRC and RECIST v1.1, or other tumor-specific criteria. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and biopsy on study. Patients also undergo blood sample collection on study. After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and then every 3 months thereafter.
研究者
入排标准
入选标准
- •Histologically or pathologically confirmed malignancy (hematologic or solid tumor) that is metastatic or unresectable and for which standard of care therapy does not exist or is no longer effective
- •ACT infusion prior to study enrollment (cohorts include ACT with tumor infiltrating lymphocytes \[TIL\], human leukocyte antigen \[HLA\]-class I T cell receptor \[TCR\]-engineered lymphocytes, HLA-class II TCR-engineered lymphocytes, and chimeric antigen receptor \[CAR\]-engineered T cells)
- •Prior ACT therapy should be completed, and residual disease documented by either radiographic progression or active disease observed on biopsy (i.e. hematologic or solid tumor malignancy must be deemed active by the treating investigator); the investigator may deem that the disease is active on the basis of a pre-treatment biopsy demonstrating viable tumor cells or clinical progression of disease (i.e. RECIST progression is not required)
- •Solid tumor patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 15 mm (\>= 1.5 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- •Leukemia and non-Hodgkin's lymphoma patients must have measurable disease according to the revised response criteria for malignant lymphoma
- •Disease suitable for assessment by pre- and post-biopsies
- •There is no limit to the number of lines of prior therapy; prior anti-programmed cell death (PD)-1 or anti-PD-ligand (L)1 therapy and other immunotherapies are allowed
- •Prior anti-PD-1 or anti-PD-L1 therapy may not be administered after ACT and before study atezolizumab (MPDL3280A) administration
- •All ACT related toxicities resolved to grade 1 with the exception of alopecia, vitiligo and endocrine abnormalities requiring replacement therapy which may be grade 2
- •No prior other anti-cancer therapy, including ACT, for 28 days prior to study administration of atezolizumab
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier; however, the following therapies are allowed:
- •Hormone-replacement therapy or oral contraceptives
- •Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
- •Palliative radiotherapy for bone metastases \> 2 weeks prior to cycle 1, day 1
- •Patients who have received prior treatment with anti-CTLA-4 antibody may be enrolled, provided the following requirements are met:
- •\> 6 weeks from the last dose
- •No history of severe immune-related adverse effects from anti-CTLA-4 antibody (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] grade 3 and 4)
- •Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
- •Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
研究组 & 干预措施
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Laboratory Biomarker Analysis
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Atezolizumab
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Biopsy Procedure
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Treatment (atezolizumab)
Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 6 weeks
Will be assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 (CTCAE version 5.0 will be used starting 04/01/2018). Adverse experiences will be graded and recorded throughout the study and during the follow-up period.
次要结局
- Anti-tumor activity(Up to 1 year)
- Expansion of engrafted T cells following atezolizumab administration in the peripheral blood and within the tumor microenvironment(Up to 1 year)
- The response rate(Up to 1 year)
- Survival outcomes(Up to 1 year)
- Progression free survival(Up to 1 year)
- Biomarker analysis(Up to 1 year)
- Phenotype and function of engrafted T cells following atezolizumab administration(Up to 1 year)