Dendritic Cell Therapy After Cryosurgery in Combination With Pembrolizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Remove by Surgery

This is an interventional treatment trial for Stage III Cutaneous Melanoma AJCC v7 Read More

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to curative local therapy
• Documented progression of disease after initiation of therapy with OR lack of response to therapy with a PD-1- or PD-L1-targeting monoclonal antibody (pembrolizumab, nivolumab, etc) after at least 18 weeks; NOTE: This treatment could have been at any time prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

• Minimum of 3 radiographically apparent lesions such that there is:

  • Minimum of one lesion in areas that have not been previously irradiated that is considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria AND
  • Minimum of two lesions in areas that have not been previously irradiated that are determined by interventional radiology to be of a size and in a location that a single probe could ablate at least 75% of the lesion; Note: Hepatic lesions measuring =< 3 cm may be treated, as determined by interventional radiology; Note: Brain metastases are not acceptable as lesions defining measurable disease, nor are they candidate lesions for cryoablation
• Adequate venous access for apheresis as assessed by apheresis team; NOTE: If a central venous catheter is required for apheresis, the patient is not eligible
• Absolute neutrophil count (ANC) >= 1000/mm^3 obtained =< 14 days prior to registration
• Absolute lymphocyte count >= 500/mm^3 obtained =< 14 days prior to registration
• Platelet count >= 100,000/mm^3 obtained =< 14 days prior to registration
• Hemoglobin >= 10 g/dL obtained =< 14 days prior to registration
• Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert?s disease obtained =< 14 days prior to registration
• Aspartate transaminase (AST/(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN obtained =< 14 days prior to registration
• Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 mL/min for subject with creatinine ? 1.5 x institutional ULN obtained =< 14 days prior to registration
• Negative serum pregnancy test for persons of childbearing potential =< 7 days prior to registration
• Provide written informed consent
• Willing to return to the enrolling institution for follow-up (during active treatment and active monitoring phase of the study)
• Willing to provide tissue and blood samples for research purposes
• Willing to use adequate contraception while on the study and until 120 days after the last dose of study drug

Exclusion Criteria:

• Any of the following:

  • Pregnant persons
  • Nursing persons
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Active tuberculosis or active, non-infectious pneumonitis
• Evidence of interstitial lung disease
• Active infection requiring the use of systemic antibiotics
• Symptomatic congestive heart failure (New York Heart Association classification III or IV cardiovascular disease, myocardial infarction =< 6 months prior to registration, unstable angina pectoris or cardiac arrhythmia =< 3 months prior to registration, or cardiac arrhythmia
• Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =< 21 days prior to registration
• History of other primary malignancy requiring systemic treatment =< 3 years prior to registration; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
• Failure to recover from prior side effects of immune checkpoint inhibitor therapy to =< grade 1; NOTE: Patients will not be excluded for adrenal insufficiency or hypothyroidism secondary to immunotherapy provided they are receiving hormonal replacement
• Major surgery =< 4 weeks prior to registration
• Prior chemotherapy, targeted therapy, or radiation therapy =< 2 weeks prior to registration or who has not recovered (i.e. to =< grade 1 or baseline) from an adverse event due to the previously administered therapy
• History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid

• Active autoimmune disease such as Crohn?s disease, rheumatoid arthritis, Sjogrens? disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past; EXCEPTIONS (the following are allowed):

  • Vitiligo or resolved childhood asthma/atopy
  • Intermittent use of bronchodilators or local steroid injections
  • Hypothyroidism stable on hormone replacement
  • Diabetes stable with current management
  • History of positive Coombs test but no evidence of hemolysis
  • Psoriasis not requiring systemic treatment
  • Conditions not expected to recur in the absence of an external trigger
  • Secondary adrenal insufficiency from previous hypophysitis, currently on physiologic replacement steroid dosing only
• Coagulopathy, including the use of therapeutic anticoagulants that cannot be discontinued for the cryoablation procedure; NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed
• Corticosteroid use =< 14 days prior to registration; NOTE: Patients must be off systemic corticosteroids for at least 2 weeks prior to registration; this includes oral or IV route of administration; patients on chronic corticosteroids for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent); patients receiving inhaled or intranasal or intra-articular steroids are not excluded
• Active central nervous system (CNS) metastasis; NOTE: Patients with prior brain metastases that are asymptomatic without corticosteroid use and stable or improved >= 90 days after treatment with surgery or radiation are not excluded
• Receipt of a live vaccine =< 30 days prior to registration