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

NCT04093323 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: I 82419NCI-2019-05911P01CA234212
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well polarized dendritic cell (aDC1) based therapy, 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 cell-based treatment 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 the combination of the study cell-based treatment (aDC1 dendritic cells) and interferon alpha-2, rintatolimod, and celecoxib can prevent the growth and/or progression of melanoma.

Conditions

Refractory Melanoma; HLA-A2 Positive Cells Present

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be carried out by an exact binomial test of a proportion within a Simon two-stage design.

  At 12 weeks

Secondary Outcomes (2)

• ORR

  At 6 months

• Durable Objective Response Rate (>= 6 Months)

  From time of first confirmed response assessed up to 2 years

Other Outcomes (4)

• Immune-related Progressive Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

• Change in Density of CD8 Positive Cytotoxic T Cells

  Baseline up to week 11

Study Arms (1)

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

EXPERIMENTAL

Patients receive recombinant interferon alpha-2 IV over 30 minutes, rintatolimod IV over 2.5 hours, and celecoxib PO BID on days 1-3. Beginning cycle 2, patients also receive alpha-type-1 polarized dendritic cells ID on day 1. Treatment repeats every 3 weeks up to 4 cycles in the absence of disease progression or unacceptable toxicity. At 12 weeks, patients with progressive disease may switch to ipilimumab with or without a PD-1/PD-L1 inhibitor and patients with a complete response CR, PR, or stable disease SD may switch to a PD-1/PD-L1 inhibitor or best alternative care.

Biological: Alpha-type-1 Polarized Dendritic Cells; Drug: Celecoxib; Drug: PD-1 Ligand Inhibitor; Drug: PD1 Inhibitor; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

Interventions

Alpha-type-1 Polarized Dendritic Cells BIOLOGICAL

Given ID

Also known as: alphaDC1

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

PD-1 Ligand Inhibitor DRUG

Given IV

Also known as: PD-1 Ligands Inhibitor

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

PD1 Inhibitor DRUG

Given IV

Also known as: PD-1 Inhibitor, Programmed Cell Death Protein 1 Inhibitor, Protein PD-1 Inhibitor

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

Recombinant Interferon Alfa-2b BIOLOGICAL

Given IV

Also known as: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Interferon Alfa-2B, Interferon Alpha-2b, Intron A, Sch 30500, Urifron, Viraferon

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

Rintatolimod DRUG

Given IV

Also known as: Ampligen, Atvogen

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

Celecoxib DRUG

Given PO

Also known as: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 cell based treatment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Celecoxib; Immune Checkpoint Inhibitors; Introns; Interferon alpha-2; poly(I).poly(c12,U)

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

The study was terminated. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

Adrienne.Groman@RoswellPark.org

7168451300

Study Officials

• Igor Puzanov

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 18, 2019
• Study Start: November 13, 2024
• Primary Completion: April 3, 2025
• Study Completion: June 19, 2025
• Last Updated: February 25, 2026
• Results First Posted: February 25, 2026

Record last verified: 2026-02

Locations

US (1)