Clinical Trials /

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

NCT04093323

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Polarized Dendritic Cell (aDC1) Vaccine, Interferon Alpha-2, Rintalolimid, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma
  • Official Title: A Phase II Study of Type-1 Polarized Dendritic Cell (aDC1) Vaccine in Combination With Tumor-Selective Chemokine Modulation (CKM: Interferon Alpha 2b, Rintatolimod and Celecoxib) in Melanoma Patients With Primary PD-1/PD-L1 Resistance

Clinical Trial IDs

  • ORG STUDY ID: I 82419
  • SECONDARY ID: NCI-2019-05911
  • SECONDARY ID: I 82419
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT04093323

Conditions

  • HLA-A2 Positive Cells Present
  • Refractory Melanoma

Interventions

DrugSynonymsArms
Alpha-type-1 Polarized Dendritic CellsalphaDC1Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)
CelecoxibBenzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)
PD-1 Ligand InhibitorPD-1 Ligands InhibitorTreatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)
PD1 InhibitorPD-1 Inhibitor, Programmed Cell Death Protein 1 Inhibitor, Protein PD-1 InhibitorTreatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)
Recombinant Interferon Alfa-2bAlfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Interferon Alfa-2B, Interferon Alpha-2b, Intron A, Sch 30500, Urifron, ViraferonTreatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)
RintatolimodAmpligen, AtvogenTreatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the objective response rate to treatment with an autologous alpha-type-1
      polarized dendritic cells (alphaDC1)/TBVA vaccine (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.

      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 vaccine plus cytokine CKM regimen followed
      by re-treatment with PD1 blockade (+/- CTLA4 blockade).

      II. Evaluate rate of durable responses (> 6 months) on the combination treatment in the above
      patient population treated with autologous alphaDC1/TBVA vaccine plus cytokine CKM regimen
      followed by re-treatment with PD1 blockade (+/- CTLA4 blockade).

      EXPLORATORY OBJECTIVES:

      I. Examine whether the combination of peptide-loaded autologous alphaDC1 vaccines 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (IFNA2, rintatolimod, celecoxib, alphaDC1 vaccine)ExperimentalPatients 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.
  • Alpha-type-1 Polarized Dendritic Cells
  • Celecoxib
  • PD-1 Ligand Inhibitor
  • PD1 Inhibitor
  • Recombinant Interferon Alfa-2b
  • Rintatolimod

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:At 12 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:ORR
Time Frame:At 6 months
Safety Issue:
Description: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) vaccine 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.
Measure:Durable objective response rate (>= 6 months)
Time Frame:From time of first confirmed response assessed up to 2 years
Safety Issue:
Description:Will be evaluated on patients treated autologous alphaDC1/TBVA vaccine 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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated