Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma

Launched by ROSWELL PARK CANCER INSTITUTE · Sep 16, 2019

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment approach for patients with a specific type of melanoma that has not responded to previous therapies, known as refractory melanoma. The treatment combines a specialized type of immune cell therapy, called polarized dendritic cells (aDC1), with other medications, including interferon alpha-2, rintatolimod, and celecoxib. The goal is to see if this combination can help slow down or stop the growth of melanoma in patients who have a certain genetic marker (HLA-A2 positive) that makes them eligible for the trial.

To participate, patients must have HLA-A2 positive melanoma that has resisted earlier treatments, including specific immune therapies. They should have at least one tumor that can be tested and meet other health criteria to ensure their safety during the trial. Participants will receive the study treatment and will be monitored closely for any effects. It's essential for potential participants to understand the nature of the study and agree to follow the trial's guidelines. If you or a loved one are considering joining this trial, it is a chance to explore a new treatment option that might be beneficial.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • Participant must be HLA-A2+. Retesting is not required for patients who have previous documented positivity
• • Have IO-refractory melanoma with primary PD-1/PD-L1resistance. Note: Any lines of prior therapies are allowed, but the last line needs to include an anti PD-1 or anti PD-L1 agent. The prior treatments may include any standard and/or experimental therapies
• • Have \>= 1 tumor site amenable to core needle biopsy that is not the site of disease used to measure antitumor response
• • Have measurable disease based on RECIST 1.1 criteria present
• • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• • Platelets \>= 75,000/microliter
• • Hemoglobin \>= 9 g/deciliter
• • Absolute neutrophil count (ANC) \>= 1500/microliter
• • Creatinine \< 1.5 x institutional upper limit of normal (ULN) OR creatinine clearance \>= 50 mL/min by Cockcroft-Gault formula for subjects with creatinine levels \>= 1.5 x ULN
• • Total bilirubin not greater than 1.5 x institutional ULN, except for patients with known Gilbert's Syndrome, who are eligible to no more than 2 x institutional ULN
• • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) no greater than 3 x institutional ULN OR, no greater than 5 x ULN for subjects with liver metastases
• • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• • Candidate for continuation/resumption of anti-PD-1/PD-L1 blockade (in parallel to DC vaccine and CKM)
• Exclusion Criteria:
• • Is currently being treated with systemic immunosuppressive agents, including steroids: Subjects will be ineligible until 3 weeks after removal from immunosuppressive treatments, except when they are administered as replacement therapy for endocrine dysfunction (and receive no more than 10 mg prednisone or equivalent: inhaled steroids are allowed)
• • Has had prior anti-cancer therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., no more than grade 1 or at baseline) from adverse events due to a previously administered agent, except for neuropathy (no more than grade 2) or alopecia or vitiligo (any grade)
• • Has a known additional malignancy that is progressing or requires active treatment
• • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Treated brain metastases are allowed, if stable for more than 4 weeks (and receive no more than 10 mg prednisone or equivalent: inhaled steroids are allowed).
• • Has a history of cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia (within 3 months of signing consent) or, subject has a New York Heart Association classification of III or IV
• • Has an active infection requiring systemic therapy
• • Has known active hepatitis B or hepatitis C infection
• • Has known immunosuppressive disease (e.g. human immunodeficiency virus \[HIV\], acquired immunodeficiency syndrome \[AIDS\] or other immune depressing disease). Testing is not mandatory
• • Has known serious hypersensitivity reactions to pegylated (peg)-interferon alpha-2b or interferon alpha-2b
• • Prior allergic reaction or hypersensitivity to sulfonamides, celecoxib, or nonsteroidal anti-inflammatory drugs (NSAIDs)
• • Has received a blood transfusion in the two weeks prior to leukapheresis
• • Women of child bearing potential who are pregnant or nursing
• • Unwilling or unable to follow protocol requirements
• • Any condition which in the Investigator's opinion deems the participant an unsuitable candidate or unacceptable risk to receive study drug regimen
• • Patients who showed initial response to PD-1/PD-L1 blockade and developed secondary resistance