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

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies how well polarized dendritic cell (aDC1) vaccine, interferon alpha-2, rintatolimod, and celecoxib work together in treating patients with HLA-A2 positive (+) melanoma that has not responded to previous treatment (refractory). The aDC1 vaccine contains white blood cells (dendritic cells or DCs) that stimulates the immune system. Interferon alpha-2 can improve the body?s natural response to infections and other diseases. It can also interfere with the division of cancer cells and slow tumor growth. Rintalolimid may stimulate the immune system. Celecoxib is a drug that reduces pain. This study is being done to find out if aDC1 vaccine, interferon alpha-2, rintatolimod, and celecoxib can prevent the growth and/or progression of melanoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Benzenesulfonamide; Celecoxib; Immune Checkpoint Inhibitors; Interferon alpha-2; Interferon-alpha; Interferons; Poly I-C; poly(I).poly(c12,U); Vaccines

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 PD1-resistance. 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 or legal representative 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 resumption of anti-PD1/PD-L1 or anti-CTLA4 therapy

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

• 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 PD1 blockade and developed secondary resistance