Part 1
Inclusion Criteria:
- - Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of
0, 1, or 2.
- - Patient must have one of the following histologically or cytologically documented
measurable (may be measureable by tumor markers only, such as quantitative RT-PCR
for WT1 transcript for AML, or CA-125 for ovarian carcinoma) advanced stage
malignancies: non-small cell lung, ovarian, glioblastoma, and AML (not including
acute promyelocytic leukemia), known to overexpress the WT1 protein.
- - Patient must qualify with a study specific HLA typing assay.
- - Haematological parameters:
- Absolute neutrophil count (ANC) ≥ 1,000/μl.
- - Platelet count ≥ 10.0x10(to the 4th power)/μl (≥ 5.0 x 10(to 4th power)/μl
after stem cell transplant)
- Hemoglobin ≥ 9.0 g/dL.
- - Absolute lymphocyte count (ALC) ≥ 1,000/μl (≥ 500/μl after stem cell
transplant) Note: After completion of dose escalation, patients with AML are
not required to meet these hematologic criteria.
- - Biochemical Parameters:
- serum creatinine of ≤ 1.5x upper limit of normal (ULN) for the reference lab.
- - total bilirubin of ≤ 2.0 mg/dl (≤ 3.0 mg/dl for patients with known Gilbert's
syndrome)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times
the ULN for the reference lab.
- - Patient must have access to archival tumor tissue sample or agree to undergo biopsy
after study eligibility has been confirmed to obtain fresh sample for evaluation of
WT1 expression.
In place of archival tumor tissue samples, subjects with AML should
have available a bone marrow aspirate and/or, bone marrow biopsy, with PCR for WT1
transcript performed before the first dose of study drug.
Note: The archived tumor tissue sample does not need to be delivered to the clinical site
prior to enrollment of the patient, however its availability should be confirmed through
provision of the accession number or other identification number.
Patient Inclusion Criteria
- - Part 2:
- Patient or his or her legal representatives must give written informed consent and
privacy authorization prior to participation in the study.
- - Patient must be willing and able to comply with the study procedures and visit
schedules and must be able to follow verbal and written instructions.
- - Patient must be ≥ 18 years of age.
- - Women of childbearing potential and men with female sexual partners of childbearing
potential must agree to abstain from sexual intercourse or use a double barrier
method to determine if a woman is of childbearing potential
(http://www.
nccn.org/professionals/physician_gls/f_guidelines.asp).
- - Patient must have an ECOG Performance Score of 0, 1, or 2 (refer to Appendix II).
- - Patient has a life expectancy of at least 4 months.
- - Patient must have histologically or cytologically documented measurable (may be
measurable by tumor markers only, such as quantitative RT-PCR for WT1 transcript for
AML) advanced stage glioblastoma or AML (not including acute promyelocytic
leukemia), known to overexpress the WT1 protein.
Note: Determination of WT1
expression will not be assessed prior to patient enrollment.
- - Patient must have an advanced stage malignancy defined as meeting at least one of
the following criteria:
- progressed or recurred despite standard therapy.
- - no standard therapy exists.
- - patient is intolerant of standard therapy.
- - patient is not a candidate for standard therapy.
- - Patient must be HLA-A*0201+ and/or HLA-A*0206+
- Patient with glioblastoma must have adequate bone marrow and immune reserve, as
documented by:
- ANC ≥ 1000/μl (≥ 500/μl after stem cell transplant)
- Platelet count ≥ 10.0 x 1(to the 4th power)/μl (≥ 5.0 x 10(to the 4th power)/μl
after stem cell transplant)
- Hemoglobin ≥ 9.0 g/dL.
- - ALC ≥ 900/μl (Note: Patients with AML are not required to meet these hematologic
criteria).
- - Patient must have adequate renal function documented by a serum creatinine of ≤ 1.5
times the ULN for the reference lab.
- - Patient must have adequate hepatic function documented by a total bilirubin of ≤ 2.0
mg/dl (≤ 3.0 mg/dl for patients with known Gilbert's syndrome) and ALT and AST ≤ 3
times the ULN for the reference lab.
- - Patient must have access to archival tumor tissue sample or agree to undergo biopsy
after study eligibility has been confirmed to obtain fresh sample for evaluation of
WT1 expression.
In place of archival tumor tissue samples, patients with AML should
have available a bone marrow aspirate and/or bone marrow biopsy with PCR for WT1
transcript performed before the first dose of study drug.
Note: The archived tumor tissue sample does not need to be delivered to the clinical site
prior to enrollment of the patient, however its availability should be confirmed through
provision of the accession number or other identification number.
• Patients with AML must be willing to undergo bone marrow aspiration/biopsy during
treatment if there are no other indicators of measureable disease.
Part 1
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 Exclusion Criteria
- - Part 2:
- 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
