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About
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.
Full description
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.
Enrollment
Sex
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Volunteers
Inclusion criteria
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
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
Age >= 18 years. Because no dosing or adverse event data are currently available on the use of atezolizumab in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Life expectancy of greater than 3 months
Absolute neutrophil count >= 1,000/mcL
Platelets >= 75,000/mcL (>= 50,000 for patients with hematologic malignancies)
Hemoglobin >= 8 g/dL
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (AST and/or ALT =< 5 x ULN for patients with liver involvement)
Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
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:
Patients who have received prior treatment with anti-CTLA-4 antibody may be enrolled, provided the following requirements are met:
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
Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Patients with known clinically significant liver disease (have previously tested positive), including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
History or risk of autoimmune disease that threatens vital organ function, including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barre syndrome, multiple sclerosis, or glomerulonephritis
Patients with a prior history of immune related events to anti-CTLA-4 may be eligible after discussion with the sponsor; however, patients with a history of grade 3 and 4 pulmonary, CNS and renal events attributed to anti-CTLA-4 agents will be excluded
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
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
Patients who have previously tested positive for human immunodeficiency virus (HIV) are NOT excluded from this study (please note: testing of all patients wishing to enroll is NOT required), but HIV-positive patients must have:
Pregnant women are excluded from this study because atezolizumab is PD-L1 blocking agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab
Primary purpose
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Interventional model
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40 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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