Atezolizumab in Treating Patients With Cancer Following Adoptive Cell Transfer

Age Range:18 - Any
Start Date:February 23, 2017
End Date:November 21, 2020

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A Pilot Study of Atezolizumab (MPDL3280A) Following Adoptive Cell Transfer in Active Hematologic or Solid Tumor Malignancies

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.


I. To evaluate the safety of atezolizumab (MPDL3280A) administration in patients who have
received adoptive cell transfer (ACT) within 6 months of enrollment.


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

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.


Patients receive atezolizumab intravenously (IV) over 30- 60 minutes on day 1. Courses repeat
every 21 days for a total of 17 doses over up to 12 months in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and then
every 3 months thereafter.

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

- Prior ACT infusion within 6 months of 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

- No prior other anti-cancer therapy, including ACT, for 28 days prior to study
administration of atezolizumab

- 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)

- 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

- 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:

- 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

- Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea, premedication for
a radiologic contrast allergy) may be enrolled

- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension or adrenocortical insufficiency is

- Patients who receive low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed

- Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of
bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is

- 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:

- There are no more than 3 lesions, =< 1 cm in size each

- Evaluable or measurable disease outside the CNS

- No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
10 mm of the optic apparatus (optic nerves and chiasm)

- No history of intracranial hemorrhage or spinal cord hemorrhage

- No ongoing requirement for dexamethasone for CNS disease; patients on a
stable dose of anticonvulsants are permitted

- No neurosurgical resection or brain biopsy within 28 days prior to cycle 1,
day 1

- Patients with asymptomatic treated CNS metastases may be enrolled, provided all
the criteria listed above are met as well as the following:

- Radiographic demonstration of improvement upon the completion of CNS
directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study

- No stereotactic radiation or whole-brain radiation within 28 days prior to
cycle 1, day 1

- Screening CNS radiographic study >= 4 weeks from completion of radiotherapy
and >= 2 weeks from discontinuation of corticosteroids

- 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

- Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible

- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)

- 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:

- Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations

- Rash must cover less than 10% of body surface area (BSA)

- Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)

- No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)

- 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

- Influenza vaccination should be given during influenza season only (approximately
October to March); patients must not receive live, attenuated influenza vaccine
within 4 weeks prior to cycle 1, day 1 or at any time during the study

- 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:

- A stable regimen of highly active anti-retroviral therapy (HAART)

- No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections

- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard
PCR-based tests

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with atezolizumab
We found this trial at
550 Peachtree St NE
Atlanta, Georgia 30308
(404) 686-4411
Principal Investigator: Jonathon B. Cohen
Phone: 888-946-7447
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
Atlanta, GA
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Atlanta, Georgia 30322
Principal Investigator: Jonathon B. Cohen
Phone: 404-778-1868
Atlanta, GA
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Atlanta, Georgia 30342
Principal Investigator: Jonathon B. Cohen
Phone: 888-823-5923
Atlanta, GA
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Columbus, Ohio 43210
Principal Investigator: Samantha M. Jaglowski
Phone: 800-293-5066
Columbus, OH
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Houston, Texas 77030
Principal Investigator: David S. Hong
Phone: 877-312-3961
Houston, TX
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3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
Principal Investigator: Aaron Goodman
Phone: 858-822-5354
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
La Jolla, CA
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Tampa, Florida 33612
Principal Investigator: Frederick L. Locke
Phone: 800-456-7121
Tampa, FL
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Toronto, Ontario
Principal Investigator: Marcus O. Butler
Phone: 416-946-4501
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