Clinical Study of WT2725 in Patients With Advanced Malignancies

Exclusion Criteria

• •Patient with an extensively disseminated primary glioblastoma.
• •Patient with symptomatic brain metastases, ie, not neurologically stable or requiring treatment with corticosteroids, or central nervous system (CNS) leukemia.
• •Patient with an infection requiring treatment with systemic antibiotics or antiviral medication or has completed treatment for such an infection within 4 days prior to planned initial dose of WT2725.
• •Patient requiring systemic, pharmacologic doses of corticosteroids (equivalent to \> 60 mg hydrocortisone/day or 2 mg dexamethasone/day). Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed.
• •Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, human immunodeficiency virus (HIV)-1, or HIV-2 antibody, or has a history of a positive result.
• •Patient has received any of the following treatments within the specified timeframe prior to dosing:
• •* endocrine therapy, immunotherapy, transfusion, hematopoietic factors within 14 days prior to planned first dose of study drug (Note: After completion of dose escalation, patients with AML are not required to meet these hematologic criteria, eg. transfusions and hematopoietic growth factors.)
• •* chemotherapy including molecular-targeting therapy within 21 days (for molecular-targeted agents that are not associated with myelosuppression or immunosuppression, the minimum interval is 5 half-lives if that is less than 21 days)
• •* surgery, radiation, or immunosuppressants within 28 days
• •* investigational drug within 28 days
• •* mitomycin-C or nitrosoureas within 42 days
• •Patient with an unresolved ≥ Grade 2 AE from a previous antineoplastic treatment, excluding alopecia.
• •Pregnant or lactating women
• •Patient with an autoimmune condition
• •Patients with serious unstable medical illness
• •Patient with pleural effusion, ascites, or pericardial fluid requiring drainage.
• •Patient is a staff member of the sponsor or clinical site and is involved in the conduct of the study or the relative of such a staff member.
• •Patient has an extensively disseminated primary glioblastoma.
• •Patient has symptomatic brain metastases, ie, presence of neurological symptoms or requiring treatment with corticosteroids, or CNS leukemia.
• •Patient has an infection and has had a body temperature of \> 38.3˚C within 48 hours prior to planned first dose of study drug.
• •Patient requires systemic, pharmacologic doses of corticosteroids (equivalent to \> 60 mg hydrocortisone/day or 2 mg dexamethasone/day). Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed.
• •Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, HIV-1, or HIV-2 antibody, or has a history of a positive result.
• •Patient has received any of the following treatments within the specified timeframe:
• •* endocrine therapy, immunotherapy, transfusion, or hematopoietic factors within 14 days prior to planned first dose of study drug (Note: Patients with AML are not required to meet these hematologic criteria, eg, transfusions and hematopoietic growth factors.),
• •* chemotherapy including molecular-targeting therapy within 21 days prior to planned first dose of study drug (for molecular-targeted agents that are notis 5 half-lives if that is less than 21 days),
• •* surgery, radiation, or immunosuppressants within 28 days prior to planned first dose of study drug,
• •* investigational drug within the 28 days prior to planned first dose of study drug, or
• •* mitomycin-C or nitrosoureas within 42 days prior to planned first dose of study drug.
• •Note: Patients receiving LHRH agonists or antagonists or antiestrogens or aromatase inhibitors started and at a stable dose for at least 90 days prior to planned first dose of study drug are eligible. Patients are permitted one 28 day cycle of concurrent treatment with hydroxyurea during the study.
• •Patient has an unresolved ≥ Grade 2 AE from a previous antineoplastic treatment, excluding alopecia.
• •Woman who is pregnant or lactating or has a positive pregnancy test at screening. If a woman has a positive pregnancy test, further evaluation may be conducted to rule out ongoing pregnancy to allow the patient to be eligible.
• •Patient has an autoimmune condition, including, but not limited to, multiple sclerosis, Grave's disease, vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, myasthenia gravis, ankylosing spondylitis, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, psoriasis requiring systemic therapy, pemphigus, temporal arteritis, dermatomyositis, Sjögren's syndrome, Goodpasture's syndrome, interstitial pneumonitis, interstitial nephritis, or Henoch-Schönlein purpura.
• •Patient has in the opinion of the investigator any intercurrent conditions that could preclude their participation in the study, pose an undue medical hazard, or that could interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (NYHA Class III or IV; refer to Appendix III), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior 6 months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than2 medications for adequate control, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months.
• •Patient has pleural effusion, ascites, or pericardial fluid requiring drainage. Note: Patient who had drain removal ≥ 14 days prior to planned first dose of study drug and has no sign of worsening is eligible.
• •Patient has any other medical, psychiatric, or social condition, including substance abuse that in the opinion of the investigator would preclude participation in the study.
• •Patient has had previous treatment with the study drug or other WT1-related vaccine therapy.
• •Patient has a known hypersensitivity to any of the components of the study drug.
• •Patient is a staff member of the sponsor or clinical site and is involved in the conduct of the study or the relative of such a staff member