Clinical Trials /

Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma

NCT03617328

Description:

This study evaluates whether it is safe to administer a peptide vaccine (6MHP) with adjuvants and the CDX-1127 monoclonal antibody, and whether the adjuvants and the CDX-1127 monoclonal antibody boost immune responses to the vaccine. In this study, the adjuvants are Montanide ISA-51 and polyICLC. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and tissue from a vaccine site.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma
  • Official Title: Evaluation of Safety and Durable Immunogenicity of Melanoma Vaccination, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 20085
  • NCT ID: NCT03617328

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
6MHP6 melanoma helper peptide vaccineArm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127
Montanide ISA-51Arm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127
polyICLCArm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127
CyclophosphamideArm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127
CDX-1127VarlilumabArm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127

Purpose

This study evaluates whether it is safe to administer a peptide vaccine (6MHP) with adjuvants and the CDX-1127 monoclonal antibody, and whether the adjuvants and the CDX-1127 monoclonal antibody boost immune responses to the vaccine. In this study, the adjuvants are Montanide ISA-51, polyICLC and cyclophosphamide. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and tissue from a vaccine site.

Trial Arms

NameTypeDescriptionInterventions
Arm A: 6MHP/Montanide ISA-51 + polyICLC + mCy + CDX-1127Experimental200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously/intradermally on days 1, 8, 15, 36, 57 and 78. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. Cyclophosphamide (50 mg) will be taken orally once a day for 7 days followed by a 7 day rest period. This will be repeated for 5 cycles. Cycles will begin on the following days: Day -6 (Cycle 1) Day 8 (Cycle 2) Day 22 (Cycle 3) Day 36 (Cycle 4) Day 50 (Cycle 5) CDX-1127 (3mg/kg) will be administered intravenously on days -6, 36, and 78.
  • 6MHP
  • Montanide ISA-51
  • polyICLC
  • Cyclophosphamide
  • CDX-1127
Arm B: 6MHP/Montanide ISA-51 + polyICLC + mCyExperimental200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously/intradermally on days 1, 8, 15, 36, 57 and 78. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. Cyclophosphamide (50 mg) will be taken orally once a day for 7 days followed by a 7 day rest period. This will be repeated for 5 cycles. Cycles will begin on the following days: Day -6 (Cycle 1) Day 8 (Cycle 2) Day 22 (Cycle 3) Day 36 (Cycle 4) Day 50 (Cycle 5)
  • 6MHP
  • Montanide ISA-51
  • polyICLC
  • Cyclophosphamide

Eligibility Criteria

        Main Inclusion Criteria:

          1. Patients with stage IIB, IIC, III, or IV melanoma at original diagnosis or at
             restaging after recurrence, rendered clinically free of disease by surgery, other
             therapy, or spontaneous remission within 6 months prior to registration.

          2. Patients with small radiologic or clinical findings of an indeterminate nature may be
             eligible.

          3. Patients with high-risk stage IIA melanoma (by DecisionDx Melanoma test, Castle
             Biosciences, Inc., Friendswood, TX) may be eligible.

          4. Participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown
             primary melanoma. Diagnosis of melanoma must be confirmed by cytological or
             histological examination. Staging of cutaneous melanoma will be based on version 8
             AJCC staging system.

          5. Participants who have had brain metastases will be eligible if all of the following
             are true:

               -  Each brain metastasis must have been completely removed by surgery or each
                  unresected brain metastasis must have been treated with stereotactic
                  radiosurgery.

               -  No brain metastasis is > 2 cm in diameter at the time of registration.

               -  Any neurologic symptoms attributable to brain metastases have returned to
                  baseline.There is no evidence of new or enlarging brain metastases.

               -  The most recent surgical resections or gamma-knife therapy for malignant melanoma
                  must have been completed ≥ 1 week and ≤ 6 months prior to registration.

          6. ECOG performance status of 0 or 1.

          7. Ability and willingness to give informed consent.

          8. Adequate organ function

          9. Age 18 years or older at registration.

        Main Exclusion Criteria:

          1. The following medications or treatments at any time within 4 weeks of registration:

               -  Chemotherapy

               -  Interferon (e.g. Intron-A®)

               -  Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥
                  1 week and ≤ 6 months prior to registration)

               -  Allergy desensitization injections

               -  High doses of systemic corticosteroids

               -  Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)

               -  Interleukins (e.g. Proleukin®)

               -  Any investigational medication

               -  Targeted therapies specific for mutated BRAF or for MEK

          2. Nitrosoureas within 6 weeks of registration.

          3. Checkpoint molecule blockade therapy within 12 weeks of registration.

          4. Known or suspected allergies to any component of the vaccine.

          5. Previous vaccination with 6MHP.

          6. Prior treatment with CDX-1127 or other CD27 agonistic antibody.

          7. Pregnancy.

          8. HIV positivity or evidence of active Hepatitis C virus.

          9. Female participants must not be breastfeeding.

         10. A medical contraindication or potential problem in complying with the requirements of
             the protocol in the opinion of the investigator.

         11. New York Heart Association classification as having Class III or IV heart disease.

         12. Uncontrolled diabetes, defined as having an HgbA1c > 8.5%.

         13. Prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or
             autoimmune disorders with visceral involvement. Participants with an active autoimmune
             disorder requiring these therapies are also excluded.

         14. Participants with known addiction to alcohol or drugs who are actively taking those
             agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.

         15. Participants who have received a live vaccine within 30 days of registration.

         16. Body weight < 110 pounds at registration, due to the amount and frequency with which
             blood will be drawn.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Number of Adverse Events
Time Frame:30 days after receiving the last dose of study drug
Safety Issue:
Description:Number of Adverse Events

Secondary Outcome Measures

Measure:Immunogenicity - Number of regulatory T cells
Time Frame:Day 22 and Day 85
Safety Issue:
Description:Number of regulatory T cells in the vaccine site microenvironment
Measure:Immunogenicity - Percent of circulating regulatory T cells
Time Frame:through day 183
Safety Issue:
Description:Percent of circulating regulatory T cells responding to vaccine antigens
Measure:Immunogenicity - Frequency of circulating CD4+ Th1 responses
Time Frame:through day 183
Safety Issue:
Description:Number of participants with circulating CD4+ Th1 responses to vaccine antigens
Measure:Immunogenicity-Frequency of CD4+ Th1 memory responses
Time Frame:Day 183
Safety Issue:
Description:Number of participants with CD4+ Th1 memory response to vaccine antigens

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Craig L Slingluff, Jr

Trial Keywords

  • peptide
  • vaccine
  • adjuvant
  • cyclophosphamide
  • 6MHP
  • polyICLC
  • varlilumab
  • CDX-1127
  • Montanide ISA-51

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