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Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma (Mel-65)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03617328
Recruitment Status : Recruiting
First Posted : August 6, 2018
Last Update Posted : August 31, 2020
Sponsor:
Collaborator:
Celldex Therapeutics
Information provided by (Responsible Party):
Craig L Slingluff, Jr, University of Virginia

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Melanoma Biological: 6MHP Drug: Montanide ISA-51 Drug: polyICLC Drug: CDX-1127 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Safety and Durable Immunogenicity of Melanoma Vaccination, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma
Actual Study Start Date : November 13, 2018
Estimated Primary Completion Date : January 8, 2021
Estimated Study Completion Date : March 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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.
Biological: 6MHP
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Other Name: 6 melanoma helper peptide vaccine

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
Other Name: Varlilumab

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.
Biological: 6MHP
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Other Name: 6 melanoma helper peptide vaccine

Drug: Montanide ISA-51
Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant

Drug: polyICLC
polyICLC, local adjuvant




Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Immunogenicity - Frequency of circulating CD4+ Th1 responses [ Time Frame: through day 176 ]
    Number of participants with circulating CD4+ Th1 responses to vaccine antigens

  4. 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

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03617328


Contacts
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Contact: Adela Mahmutovic, BA 434-982-6714 am6bd@virginia.edu
Contact: Rachael Reed, BS 434-982-6584 rmr3bx@virginia.edu

Locations
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United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23284
Contact: Faith McFadden, RN, BSN    804-628-0616    mcfaddenfr@vcu.edu   
Contact: Carrie Donovan, RN    804-628-3836    donovan2@vcu.edu   
Principal Investigator: Andrew Poklepovic, MD         
Sponsors and Collaborators
Craig L Slingluff, Jr
Celldex Therapeutics
Investigators
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Principal Investigator: Craig L Slingluff, Jr., MD University of Virginia
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Responsible Party: Craig L Slingluff, Jr, Professor of Surgery; Director, Human Immune Therapy Center, University of Virginia
ClinicalTrials.gov Identifier: NCT03617328    
Other Study ID Numbers: 20085
First Posted: August 6, 2018    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Craig L Slingluff, Jr, University of Virginia:
peptide
vaccine
adjuvant
6MHP
polyICLC
varlilumab
CDX-1127
Montanide ISA-51
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers