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.
Full Title of Study: “Evaluation of Safety and Durable Immunogenicity of Melanoma Vaccination, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: January 8, 2021
- Biological: 6MHP
- 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
- Drug: Montanide ISA-51
- Montanide ISA-51 (Incomplete Freund’s Adjuvant), local adjuvant
- Drug: polyICLC
- polyICLC, local adjuvant
- Drug: CDX-1127
- CDX-1127, anti-CD27 monoclonal antibody
Arms, Groups and Cohorts
- Experimental: Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127
- 200 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. CDX-1127 (3mg/kg) will be administered intravenously on days 1, 36, and 78.
- Experimental: Arm B: 6MHP/Montanide ISA-51 + polyICLC
- 200 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.
Clinical Trial Outcome Measures
- Safety of CDX-1127 administered with a melanoma vaccine
- Time Frame: 30 days after receiving the last dose of study drug
- Number of participants with dose-limiting toxicities based on CTCAE v5.0
- Immunogenicity-Percent of patients with persistent CD4+ T cell responses to the 6MHP vaccine
- Time Frame: Day 127 or Day 176 or both
- Number of participants with CD4+ T cell responses to 6 MHP persisting to day 127 or later.
- Immunologic effect of CDX-1127 – Impact on regulatory T cells
- Time Frame: Day 22 and Day 85
- Number of regulatory T cells per mm2 in the vaccine site microenvironment
- Immunologic effect of CDX-1127 – Percent of circulating regulatory T cells
- Time Frame: through day 176
- Percent of circulating regulatory T cells among CD4+ T cells
- Immunogenicity – Frequency of circulating CD4+ Th1 responses
- Time Frame: through day 176
- Number of participants with circulating CD4+ Th1 responses to vaccine antigens
- Immunogenicity-Frequency of durable CD4+ Th1 memory responses
- Time Frame: Day 8 to Day 85
- Number of participants with durable CD4+ Th1 memory response to vaccine antigens, measured as response at two or more consecutive time points
- Immunogenicity-Frequency of CD4+ Th1 memory responses
- Time Frame: Day 183
- Number of participants with CD4+ Th1 memory response to vaccine antigens a week after the Day 176 booster vaccine.
Participating in This Clinical Trial
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:
- 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.
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.
17. Participants with prior autoimmune pneumonitis.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Craig L Slingluff, Jr
- Celldex Therapeutics
- Provider of Information About this Clinical Study
- Sponsor-Investigator: Craig L Slingluff, Jr, Professor of Surgery; Director, Human Immune Therapy Center – University of Virginia
- Overall Official(s)
- Craig L Slingluff, Jr., MD, Principal Investigator, University of Virginia
- Overall Contact(s)
- Adela Mahmutovic, BA, 434-982-6714, email@example.com
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