Phase 2 Study of Recombinant Glycosylated Human Interleukin-7 (CYT107) After Completion of Standard Therapy With Sipuleucel-T (Provenge®) in Pts w/ Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer(mCRPC)
Phase 2 Study of Recombinant Glycosylated Human Interleukin-7 (CYT107) After Completion of Standard Therapy With Sipuleucel-T (Provenge®) in Pts w/ Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer(mCRPC)
This randomized phase II trial studies how well glycosylated recombinant human interleukin-7 (CYT107) after vaccine therapy works in treating patients with castration-resistant prostate cancer that has spread to other areas of the body or has not responded to at least one type of treatment. Biological therapies, such as glycosylated recombinant human interleukin-7, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. It is not yet known whether glycosylated recombinant human interleukin-7 works better with or without vaccine therapy in treating prostate cancer.
PRIMARY OBJECTIVES:
I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to the sipuleucel-T fusion protein vaccine construct prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF) (PA2024).
SECONDARY OBJECTIVES:
I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to PAP.
II. To assess the character of the T-cell immune response to PAP and PA2024. III. To determine whether CYT107 administration increases the vaccine-induced antigen-specific antibody immune responses to PAP and PA2024.
IV. To quantify the effects of CYT107 on T-cell repertoire diversity. V. To assess the effects of CYT107 on the immune competence of patients with advanced prostate cancer.
VI. To assess the clinical efficacy and tolerability of sipuleucel-T plus CYT107 compared with sipuleucel-T alone.
OUTLINE: Patients are randomized to 1 of 2 cohorts.
COHORT I: Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy.
COHORT II: Patients receive glycosylated recombinant human interleukin-7 subcutaneously (SC) every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 53 weeks. Patients are followed by phone, once a year, after completion of Week 53 for overall survival.
Inclusion Criteria:
Exclusion Criteria:
Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy and chemotherapy given for hormone sensitive prostate cancer are allowed
Prior investigational immunotherapy
Prostate cancer pain requiring regularly scheduled narcotics
Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 30 days prior to first CYT107 injection
Known central nervous system metastases
Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion
History of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Concurrent or prior malignancy except for the following:
Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder; HIV-positive patients on combination antiretroviral therapy are ineligible
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
History of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107
Patients who have received prior immunosuppressive therapy within 30 days prior to enrollment
Active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy)
Patients who have received hepatotoxic drugs less than 7 days prior to enrollment
Patients who have received prior biologic agents less than 30 days prior to enrollment
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Patients who have a history of any hematopoietic malignancy
History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)