Clinical Trials /

Atezolizumab in Treating Patients With Cancer Following Adoptive Cell Transfer

NCT02862275

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab in Treating Patients With Cancer Following Adoptive Cell Transfer
  • Official Title: A Pilot Study of Atezolizumab (MPDL3280A) Following Adoptive Cell Transfer in Active Hematologic or Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01232
  • SECONDARY ID: NCI-2016-01232
  • SECONDARY ID: PJC-023
  • SECONDARY ID: 10014
  • SECONDARY ID: 10014
  • SECONDARY ID: UM1CA186644
  • NCT ID: NCT02862275

Conditions

  • Hematopoietic and Lymphoid Cell Neoplasm
  • Metastatic Malignant Solid Neoplasm
  • Unresectable Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (atezolizumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety of atezolizumab (MPDL3280A) administration in patients who have
      received adoptive cell transfer (ACT) within 9 months of 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.

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (atezolizumab)ExperimentalPatients 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.
  • Atezolizumab

Eligibility Criteria

        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 9 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
             2

          -  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)

          -  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:

               -  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
                  allowed

               -  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
             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:

                    -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 6 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Expansion of engrafted T cells following atezolizumab administration in the peripheral blood and within the tumor microenvironment
Time Frame:Up to 1 year
Safety Issue:
Description:Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients.
Measure:Phenotype and function of engrafted T cells following atezolizumab administration
Time Frame:Up to 1 year
Safety Issue:
Description:Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients.
Measure:Anti-tumor activity
Time Frame:Up to 1 year
Safety Issue:
Description:Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients.
Measure:The response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed using immune related Response Criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, or other tumor-specific criteria. Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients.
Measure:Survival outcomes
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed using immune related Response Criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, or other tumor-specific criteria. Survival estimates will be computed using the Kaplan-Meier method. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sided t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Measure:Progression free survival
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed using immune related Response Criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, or other tumor-specific criteria. Survival estimates will be computed using the Kaplan-Meier method. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sided t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Measure:Biomarker analysis
Time Frame:Up to 1 year
Safety Issue:
Description:Will be tailored for each cohort as continuous variables, depending on the type of adoptive cell transfer (ACT) previously administered.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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