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.
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
Interventions
Drug | Synonyms | Arms |
---|
6MHP | 6 melanoma helper peptide vaccine | Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127 |
Montanide ISA-51 | | Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127 |
polyICLC | | Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127 |
CDX-1127 | Varlilumab | Arm A: 6MHP/Montanide ISA-51 + polyICLC + 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 and polyICLC. The investigators will monitor these effects by performing tests in the
laboratory on participants' blood and tissue from a vaccine site.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127 | Experimental | 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 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. | - 6MHP
- Montanide ISA-51
- polyICLC
- CDX-1127
|
Arm B: 6MHP/Montanide ISA-51 + polyICLC | Experimental | 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. | - 6MHP
- Montanide ISA-51
- polyICLC
|
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.
17. Participants with prior autoimmune pneumonitis.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety of CDX-1127 administered with a melanoma vaccine |
Time Frame: | 30 days after receiving the last dose of study drug |
Safety Issue: | |
Description: | Number of participants with dose-limiting toxicities based on CTCAE v5.0 |
Secondary Outcome Measures
Measure: | Immunologic effect of CDX-1127 - Impact on regulatory T cells |
Time Frame: | Day 22 and Day 85 (Note: Day 85 biopsy not required for participants whose Day 85 visit would be due after IRB approval of Protocol v12-03-2020) |
Safety Issue: | |
Description: | Number of regulatory T cells per mm2 in the vaccine site microenvironment |
Measure: | Immunologic effect of CDX-1127 - Percent of circulating regulatory T cells |
Time Frame: | through day 176 |
Safety Issue: | |
Description: | Percent of circulating regulatory T cells among CD4+ T cells |
Measure: | Immunogenicity - Frequency of circulating CD4+ Th1 responses |
Time Frame: | through day 176 |
Safety Issue: | |
Description: | Number of participants with circulating CD4+ Th1 responses to vaccine antigens |
Measure: | Immunogenicity-Frequency of durable CD4+ Th1 memory responses |
Time Frame: | Day 8 to Day 85 |
Safety Issue: | |
Description: | Number of participants with durable CD4+ Th1 memory response to vaccine antigens, measured as response at two or more consecutive time points |
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 a week after the Day 176 booster vaccine. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Craig L Slingluff, Jr |
Trial Keywords
- peptide
- vaccine
- adjuvant
- 6MHP
- polyICLC
- varlilumab
- CDX-1127
- Montanide ISA-51
Last Updated
March 26, 2021