TerminatedNCT04093323Updated Feb 25, 2026Results posted

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

A Phase 2 interventional study of Alpha-type-1 Polarized Dendritic Cells and Celecoxib in HLA-A2 Positive Cells Present and Refractory Melanoma, sponsored by Roswell Park Cancer Institute. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-25.

Sponsored by Roswell Park Cancer Institute · Phase 2, Interventional, and Treatment

Why this study was terminated

Funding completed

Phase: Phase 2
Study type: Interventional
Enrollment: 1
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

PRIMARY OBJECTIVE:

I. To evaluate the objective response rate to treatment with an autologous alpha-type-1 polarized dendritic cells (alphaDC1)/TBVA cell-based treatment (alpha-type-1-polarized dendritic cells loaded with tumor blood vessel-targeting antigenic peptides) plus cytokine modulating (CKM) regimen (rintatolimod, recombinant interferon alpha-2 [IFN-alpha2b] and, celecoxib) in human leukocyte antigen (HLA)-A2+ subjects with primary PD-1 resistant immuno-oncology (IO)-refractory melanoma (who will continue the original PD-1/PD-L1 regimen for 12 weeks).

SECONDARY OBJECTIVES:

I. To evaluate the immune-related objective response rate (objective response rate [ORR]; per immune-related Response Evaluation Criteria in Solid Tumors [iRECIST];) in the above patient population treated with autologous alphaDC1/TBVA cell-based treatment plus cytokine CKM regimen followed by continued treatment with PD-1/PD-LI blockade (+/- CTLA4 blockade or LAG3 blockade).

II. Evaluate rate of durable responses (> 6 months) on the combination treatment in the above patient population treated with autologous alphaDC1/TBVA cell-based treatment plus cytokine CKM regimen followed by continued treatment with PD-1/PD-L1 blockade (+/- CTLA4 blockade or LAG3 blockade).

EXPLORATORY OBJECTIVES:

I. Examine whether the combination of peptide-loaded autologous alphaDC1 cell-based treatment and tumor-selective chemokine modulation (CKM: IFN-a2b, rintatolimod, and celecoxib) improves the overall survival (OS) and immune-related progression-free survival (iPFS) in HLA-A2+ subjects PD-1/PD-L1-refractory melanoma compared to the historical control of the best supportive care.

II. Identify the intratumoral and systemic immune correlates of the response to treatment.

OUTLINE:

Patients receive recombinant interferon alpha-2 intravenously (IV) over 30 minutes, rintatolimod IV over 2.5 hours, and celecoxib orally (PO) twice daily (BID) on days 1-3. Beginning cycle 2, patients also receive alpha-type-1 polarized dendritic cells intradermally (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), partial response (PR), or stable disease (SD) may switch to a PD-1/PD-L1 inhibitor or best alternative care.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Conditions studied

HLA-A2 Positive Cells Present
Refractory Melanoma

Browse trials for

Melanoma 3,006

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 1 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Roswell Park Cancer Institute is the lead sponsor of 412 studies on the registry; 62 are open to participants now.

Of its 38 completed or terminated interventional studies of FDA-regulated products, 21 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 1 participant (actual)

Study arms

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

BiologicalAlpha-type-1 Polarized Dendritic Cells
Given ID
Also known as: alphaDC1
DrugCelecoxib
Given PO
Also known as: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177
DrugPD-1 Ligand Inhibitor
Given IV
Also known as: PD-1 Ligands Inhibitor
DrugPD1 Inhibitor
Given IV
Also known as: PD-1 Inhibitor, Programmed Cell Death Protein 1 Inhibitor, Protein PD-1 Inhibitor
BiologicalRecombinant Interferon Alfa-2b
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
DrugRintatolimod
Given IV
Also known as: Ampligen, Atvogen

What researchers measure

Primary outcomes

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.
Time frame: At 12 weeks

Secondary outcomes

ORR
Will be evaluated using immune-related RECIST (iRECIST) criteria in patients that continue on with either PD1 and/or CTLA4 blockade after meeting the 12-week primary objective treated with autologous alpha-type-1 polarized dendritic cells (alphaDC1)/tumor blood vessel-targeting antigenic peptides (TBVA) cell-based treatment plus cytokine modulating (CKM) regimen followed by re-treatment with PD1 blockade (+/- CTLA4 blockade). The analysis will be primarily descriptive and consist of sample proportions and the corresponding 95% confidence intervals.
Time frame: At 6 months
Durable Objective Response Rate (>= 6 Months)
Will be evaluated on patients treated autologous alphaDC1/TBVA cell-based treatment plus cytokine CKM regimen followed by retreatment with PD1 blockade (+/- CTLA4 blockade). The analysis will be primarily descriptive and consist of sample proportions and the corresponding 95% confidence intervals.
Time frame: From time of first confirmed response assessed up to 2 years

Other outcomes

Immune-related Progressive Free Survival
Will be evaluated using iRECIST criteria. Will be compared to the historical control of the best supportive care and to identify the intratumoral and systemic immune correlates of the response to treatment. Will be analyzed by a Cox regression model as a function of various biomarker combinations.
Time frame: Up to 2 years
Overall Survival
Will be compared to the historical control of the best supportive care and to identify the intratumoral and systemic immune correlates of the response to treatment. Will be analyzed by a Cox regression model as a function of various biomarker combinations.
Time frame: Up to 2 years
Change in Density of CD8 Positive Cytotoxic T Cells
Will be evaluated using the OmniSeq immune report card (IRC). Will be analyzed by a Cox regression model as a function of various biomarker combinations.
Time frame: Baseline up to week 11
Change in Density of Molecular Biomarkers
Will be evaluated using the OmniSeq IRC. Will be analyzed by a Cox regression model as a function of various biomarker combinations.
Time frame: Baseline up to week 11

Results

Posted Feb 25, 2026

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.

Participant flow

Participant flow — Overall Study
Milestone	Treatment (IFNA2, Rintatolimod, Celecoxib, alphaDC1 Cell Based Treatment)
Started	0
Completed	0
Not completed	0

Outcome measures

PrimaryObjective 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.

Time frame:: At 12 weeks