Patients diagnosed with progressive and/or refractory solid malignancies, who have failed
conventional therapy, and have no available, potentially curative therapeutic options, will
be candidates for this Phase I/II study. Following confirmation of disease progression and/or
refractoriness, eligible patients who agree to participate and sign an informed consent form
will have their tumor cells/tissues and/or blood analyzed for the expression of a specific
panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1,
Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.
For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4,
PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by
phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs
will be generated in Kiromic's Cell Processing GMP facility, according to established
Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s)
relevant for each particular patient. Patients will receive five (5) days of low-dose
cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg
activity. Patients will also receive a single dose of topical Imiquimod cream after each
vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC
vaccination schedule will be weekly via intradermal (ID) injections for a total of 3
vaccinations. Topical Imiquimod cream will also be administered once after the vaccination.
Patients will be followed on a weekly basis (or more frequently if required) to evaluate
treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per
protocol specifications. Continuation and stopping rules for the study will be defined based
on toxicity/tolerability (Phase I) and immune efficacy (Phase II).
Inclusion Criteria:
1. Ability to provide informed consent.
2. Patients with histologically proven progressive and/or refractory SM, s/p conventional
salvage therapy, completed at least 3 weeks prior to study vaccination, will be
eligible for enrollment.
3. Expression of one (1) or more of the following TAPAs: Sp17, AKAP-4, Ropporin, PTTG-1,
Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1, by either RT-PCR and/or
immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood. For
HER-2/neu expression, positive FISH results are acceptable.
4. Presence of measurable or evaluable disease.
5. Patients must not have any active infectious process.
6. Patients must not have a history of HIV, or active Hepatitis A, B, and C.
7. Patients must not be receiving active immunosuppressive therapy.
8. Patients must have discontinued systemic cytotoxic or radiation therapy at least three
(3) weeks prior to vaccination and toxicities from previous therapies must be grade 1
or less. all other FDA approved forms of antineoplastic therapy are allowed such as
immunotherapy, targeted therapies, or hormonal therapies (67, 68)
9. Patients may not have any known allergy to CYP and/or Imiquimod.
10. Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood
obtained by phlebotomy and/or consent to leukapheresis for DC generation.
11. Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl,
AST and ALT ≤ 4X upper limit of normal range).
12. Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3,
neutrophils ≥ 750/mm3, hemoglobin ≥ 9.0 g/dl).
13. Karnofsky performance status ≥ 70%.
14. Expected survival ≥ 6 months.
15. Either a female or male of reproductive capacity wishing to participate in this study
must be using, or agree to use, one or more types of birth control during the entire
study and for 3 months after completing the study. Birth control methods may include
condoms, diaphragms, birth control pills, spermicidal gels or foams, anti-gonadotropin
injections, intrauterine devices (IUD), surgical sterilization, or subcutaneous
implants. Another choice is for a subject's sexual partner to use one of these birth
control methods. Women of reproductive capacity will be required to undergo a urine
pregnancy test before completion of the post-screening informed consent process.
Exclusion Criteria:
1. Patients without confirmed progressive and/or refractory SM using standard RECIST
criteria.
2. Patients without measurable or evaluable disease.
3. Patients receiving cytotoxic therapy or radiation therapy, within three (3) weeks of
vaccination.
4. Active immunosuppressive therapy, including non-physiologic systemic steroids
(excluding topical, intraocular, inhaled, and intranasal steroids) for any other
condition.
5. Persistent fever (>24 hours) documented by repeated measurement or active,
uncontrolled infection within 4 weeks of enrollment.
6. Active ischemic heart disease or history of myocardial infarction within six months.
7. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus
(SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), Inflammatory Bowel
Disease (IBD) and Rheumatoid Arthritis (RA).
8. Pregnancy or breast feeding.
9. Active second invasive malignancy, other than basal cell carcinoma of the skin.
10. Life expectancy of less than 6 months.
11. Patients with contraindications to CYP and/or Imiquimod.
12. Patients who have received organ transplants.
13. Patients with psychological or geographic conditions that prevent adequate follow- up
or compliance with the study protocol.
