Study of Atezolizumab in Relapsed or Refractory Hodgkin Lymphoma
Condition: Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Atezolizumab
Intervention description: All patients will receive atezolizumab 1200 mg via IV infusion on D1 of each 21-day cycle.
Intervention MeSH terms: Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a protocol comprised of a single institution phase II study in HL evaluating the efficacy of atezolizumab.
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; Atezolizumab; 17-191

Summary:

      This is a study with the purpose of studying the safety and efficacy of the study drug
      Atezolizumab in patients with relapsed or refractory Hodgkin lymphoma (HL). Atezolizumab
      could shrink cancer but it could also cause side effects. This study will also test any good
      and bad effects the study drug. Other aims include studying biomarkers that will help
      researchers understand how the drug works.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed Informed Consent Form (ICF)

          -  Ability and willingness to comply with the requirements of the study protocol

          -  Age ≥ 18 years

          -  Patient has histologically confirmed diagnosis of Hodgkin lymphoma

          -  Patients must have received at least 2 prior regimens and have received or be deemed
             ineligible for autologous stem cell transplant, and must have received prior
             brentuximab vedotin.

          -  Patients who received prior anti-PD-1 therapy are eligible for cohort 1 only and
             patients who have not received prior anti-PD-1 therapy are eligible for cohort 2 only.

          -  Patient has at least one measurable nodal lesion (≥ 2 cm) according to RECIL Criteria

          -  Adequate hematologic and end organ function, defined by the following laboratory
             results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):

               -  ANC ≥ 1500 cells/µL

               -  WBC counts > 2500/µL

               -  Lymphocyte count ≥ 300/µL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:

               -  Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may
                  be enrolled.

               -  AST and ALT ≤ 3.0 x ULN with the following exception:

               -  Patients with liver involvement: AST and/or ALT ≤ 5 x ULN

               -  Alkaline phosphatase ≤ 2.5 x ULN with the following exception:

               -  Patients with documented liver involvement or bone metastases: alkaline
                  phosphatase ≤ 5 x ULN

               -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of
                  the Cockcroft-Gault glomerular filtration rate estimation:

               -  (140 - age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in mg/dL)

          -  For female patients of childbearing potential and male patients with partners of
             childbearing potential, agreement (by patient and/or partner) to use highly effective
             form(s) of contraception (i.e., one that results in a low failure rate [<1% per year]
             when used consistently and correctly) and to continue its use for 90 days after the
             last dose of Atezolizumab

          -  Female subject of childbearing potential should have a negative serum pregnancy within
             28 days prior to receiving the first dose of study medication.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

        Exclusion Criteria:

          -  Patients who have undergone prior allogeneic transplant are excluded only if they
             remain on any immunosuppression or have signs or symptoms of clinical
             graft-versus-host disease

          -  Any approved anticancer therapy, including chemotherapy, hormonal therapy, or
             radiotherapy, within 3 weeks prior to initiation of study treatment.

          -  Herbal therapy (including herbal therapy intended as anticancer therapy) < 1 week
             prior to Cycle 1, Day 1

          -  AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for
             alopecia

          -  Known clinically significant liver disease

          -  Active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited
             liver disease

          -  Pregnancy, lactation, or breastfeeding

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  Inability to comply with study and follow-up procedures

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis

          -  Patients with a history of autoimmune hypothyroidism AND without normal thyroid
             hormone levels on a stable dose of thyroid replacement hormone

          -  Myocardial infarction or arterial thromboembolic events within 6 months prior to
             baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or
             IV disease, or a QTc interval > 470 msec.

          -  History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation

          -  Uncontrolled heart failure or hypertension or uncontrolled diabetes mellitus

          -  Patients with uncontrolled eczema, psoriasis, lichen simplex chronicus of vitiligo
             with dermatologic manifestations (patients without ophthalmologic involvement, rash
             covering <10% of the body surface area and requiring only low potency topical
             steroids, and without exacerbations requiring systemic therapy are eligible.)

          -  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.

          -  A history of radiation pneumonitis in the radiation field (fibrosis) is permitted
             provided that symptoms have resolved.

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complications

          -  History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C
             infection

               -  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 RNA.

          -  Patients with active tuberculosis

          -  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

          -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 for treatment
             of active infection (Patients receiving prophylactic antibiotics (e.g., for prevention
             of a urinary tract infection or chronic obstructive pulmonary disease) are eligible)

          -  Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
             infection or chronic obstructive pulmonary disease) are eligible.

          -  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

          -  Malignancies other than the disease under study within 5 years prior to Cycle 1, Day
             1, with the exception of those with a negligible risk of metastasis or death and with
             expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
             basal or squamous cell skin cancer, localized prostate cancer treated surgically with
             curative intent, or ductal carcinoma in situ treated surgically with curative intent)
             or undergoing active surveillance per standard-of-care management (e.g., chronic
             lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and
             prostate-specific antigen [PSA] ≤ 10 mg/mL, etc.)

        Medication-Related Exclusion Criteria:

          -  Prior anti-PD-L1 therapies are excluded.

             °Patients who have received prior treatment with immunotherapy including anti-PD-1
             anti-CTLA-4 may be enrolled, provided that there was no history of severe
             immune-related adverse effects (NCI CTCAE Grade 3 and 4)

          -  Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within
             five half-lives of the investigational product, whichever is longer)

          -  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) may be enrolled.

               -  The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
                  for patients with orthostatic hypotension or adrenocortical insufficiency is
                  allowed.

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins