Durvalumab for the Treatment of Relapsed or Refractory Solid Tumors, Lymphoma, or Central Nervous System Tumors

Inclusion Criteria

• Patient must have disease that is either refractory to frontline treatment or have relapsed with the following exception: * Patients with newly diagnosed, surgically incurable melanoma Patient must also have had histologic verification of a solid tumor (including lymphoma and CNS tumors) at the time of original diagnosis or relapse with the following exceptions: * Patients with germ cell tumors (both CNS and non-CNS) that have elevated tumor markers (e.g. alpha-fetoprotein, beta-human chorionic gonadotropin, inhibin A/B) and radiographic evidence of disease * Patients with diffuse intrinsic pontine glioma (DIPG) diagnosed by radiographic studies
• Patients must have either measurable or evaluable disease that can be accurately assessed at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment with the following exception: * Patients with osteosarcoma in second or greater relapse and no measurable disease following surgical resection and no subsequent medical anti-cancer therapy will be eligible for this study
• Patient’s current disease state must be one for which there is no known curative therapy
• Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Patients who are unable to walk because of paralysis, but who can actively sit up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Absolute neutrophil count >= 750/mm^3 (within 7 days prior to enrollment)
• Platelets >= 75,000/mm^3. Patients must be transfusion independent and should not have received a platelet transfusion within 5 days of enrollment (within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL. Patients may receive packed red blood cells (PRBC) transfusion (within 7 days prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70ml/min/m^2 OR a serum creatinine based on age as follows (within 7 days prior to enrollment): * Age (years): Maximum serum creatinine (mg/dL) ** < 5 years: 0.8 ** 5 to 10 years: 1 ** 10 to 15 years: 1.2 ** > 15 years: 1.5
• Total serum bilirubin =< 1.5 x upper limit of normal (ULN) for age. For patients with radiographic evidence of malignancy within the liver or patients with documented/suspected Gilbert’s disease, bilirubin =< 3 x ULN (within 7 days prior to enrollment)
• In patients with no radiographic evidence of malignancy within the liver: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 7 days prior to enrollment)
• In patients with radiographic evidence of malignancy within the liver: AST or ALT =< 5 x ULN (within 7 days prior to enrollment)
• Adequate cardiac function as indicated by shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 55% by radionuclide angiogram (within 14 days prior to the start of protocol therapy)
• Provision of signed and dated written informed consent (parent/legal guardian if patient < 18 years of age) and assent (from patients aged > 7 years) prior to any study specific procedures, sampling and analyses, including screening evaluations
• Female patients must either be of non-reproductive potential or must have a negative urine pregnancy test upon study entry
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits as well as follow up examinations

Exclusion Criteria

• Prior therapy: * Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment * Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment. Patient may be enrolled in other non-therapeutic studies * Within 14 days of the last dose of a long acting growth factor (e.g. Neulasta) or within 7 days of receiving a short acting growth factor. This does not apply to erythropoetin * Less than 3 half-lives or 28 days (whichever is shorter) after the last dose of monoclonal antibody, and without resolution of all known toxicity of the antibody * Any other chemotherapy, immunotherapy or anticancer agents within 4 weeks of the first dose of study treatment with the exception of vincristine. Patients who have received vincristine within 7 days of the first dose of study drug treatment are excluded * Any previous systemic exposure to a PD-1 or PD-L1 inhibitor, including durvalumab * Major surgery (excluding placement of vascular access and needle biopsies) within 2 weeks of the first dose of study treatment * Radiotherapy within two weeks for local palliative radiation therapy (XRT) or within 6 weeks if craniospinal XRT or if >= 50% radiation of pelvis * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of ** Intranasal and inhaled corticosteroids ** Systemic corticosteroids at physiological doses for adrenal insufficiency. For all other patients the dose must not exceed 10 mg/day of prednisone, or an equivalent corticosteroid ** Steroids as pre-medication for hypersensitivity reactions (e.g., computed tomography [CT] scan pre-medication) * Any prior allogeneic bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT) * Autologous BMT/HSCT within 90 days
• All prior acute toxicities from medical therapy or radiation therapy should resolve to meet the baseline inclusion criteria in regards to organ function requirement. All other prior acute toxicities that are not part of the baseline organ function requirements must improve to =< grade 1 and using Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.03
• Any of the following cardiac criteria: * Mean resting corrected QT interval (QTcB) > 470 msec obtained from at least 2 electrocardiograms (ECGs) * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block) * Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
• Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with hypothyroidism as a result of irradiation or thyroidectomy are also not excluded
• Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
• History of primary immunodeficiency
• Any underlying interstitial lung disease
• Brain metastases or spinal cord compression unless asymptomatic, treated and stable for at least 1 month prior to entry into the study
• Ongoing or expected need for systemic corticosteroids >= 10mg/day
• Known history of previous clinical diagnosis of tuberculosis
• Receipt of live attenuated vaccination within 30 days prior to receiving study treatment. Inactivated viruses, such as those in the influenza vaccine, are permitted
• History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
• Pregnant patients are ineligible for this study due to the unknown teratogenic effects of this agent. Pregnancy tests must be obtained in females of childbearing potential prior to enrollment
• Post-menarchal females and males who are sexually active with women of childbearing potential who are not employing/willing to employ an effective method of birth control
• Patients with serious infections or significant pulmonary, hepatic, renal, or other end-organ dysfunction which in the judgment of the principal or co-investigators would compromise the patient’s ability to tolerate prescribed chemotherapy or are likely to interfere with the study procedures or results will not be eligible
• Patient with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C defined by the following serology results: * Positive human immunodeficiency virus (HIV) antibody * Positive hepatitis B surface antigen (HBsAg) and positive hepatitis B core antibody (HBcAb) or undetectable hepatitis B (HBV) deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) testing * Positive hepatitis C (HCV) antibody or positive HCV ribonucleic acid (RNA) by quantitative PCR
• Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• History of hypersensitivity to durvalumab or any excipient