Phase IIB TL + YCWP + DC in Melanoma

A Prospective, Randomized, Blinded, Placebo-controlled, Phase IIb Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine vs Unloaded YCWP + DC and Embedded Phase I/IIa Trial With Tumor Lysate Particle Only (TLPO) Vaccine in Stage III and Stage IV (Resected) Melanoma to Prevent Recurrence.

The majority of melanoma vaccines tested to date have been antigen-specific vaccines targeting melanoma-specific or associated antigens and utilizing a variety of delivery systems and immune-adjuvants. As opposed to testing an "off the shelf" vaccine that might be able to treat a subset of patients, our approach has been personalized to the patient and applicable to all patients. Our vaccine approach consists of harnessing the most potent antigen presenting cell in the body - the dendritic cell (DC) - together with the full repertoire of tumor antigens from an individual's cancer. We have conducted phase I and II studies using an autologous DC-tumor cell fusion technique that has now been simplified into a DC-tumor cell lysate vaccine. The autologous tumor lysate (TL) is loaded into yeast cell wall particles (YCWP) that are naturally and efficiently taken up into the patient's DC. These autologous tumor lysate, particle-loaded, DC (TLPLDC) are injected intradermally (ID) monthly x 3 followed by boosters at 6, 12, and 18 months.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Placebo; Drug: TLPLDC

Detailed Description

Stage III and Stage IV (resected) melanoma patients will be identified prior to definitive surgery and screened for inclusion/exclusion criteria. Eligible patients will be counseled and consented for tissue procurement. Enrolled patients will have their disease surgically resected and a portion 1mg minimum of their melanoma sterilely frozen in provided freezing vials and storage tubes. This tissue will be shipped in liquid nitrogen shippers through FedEx to our central facility in Greenville SC and stored frozen until vaccine preparation. If patients cannot be rendered disease-free, they will be considered screen failures for this study. If melanoma is being resected from multiple locations primary and nodes two different metastatic sites then samples of each would be preferred but not mandatory.

As indicated by SoC per the National Comprehensive Cancer Network (NCCN) guidelines and determined by the treating team, if a patient is to receive systemic therapy (chemotherapy or IFN-aguidelines) and determined by the treating team, if a patient is to receive systemic therapy (chemotherapy or IFN-central facility in Greenville, SC) and stored frozen until vaccine preparation. If patients cannot be rendered disease-free, they will receive a single injection of Neupogen (G-CSF) 300 mod (or its equivalent) SQ 24-48 hrs. prior to having 70 mL of blood collected and sent to our central facility for DC isolation and preparation. Patients who cannot tolerate Neupogen, or its equivalent or refuse it, will have 120 mL of blood drawn and sent. Additional blood may be drawn if additional vaccine doses need to be made or re-made for any reason. Vaccines will be prepared by producing TL through freeze/thaw cycling and then loaded into pre-prepared YCWP. The TL-loaded YCWP will be introduced to the DC for phagocytosis thus creating the TLPLDC vaccine which will be frozen in single dose vials. Each vial will contain 1-1.5 x 106 TLPLDC and will be labeled with the patient's unique study number.

Based on their randomization, autologous TLPLDC (active vaccine) or unloaded YCWP + autologous DC (control) will be sent back to the site in a blinded fashion. Regardless of assigned group, the site will receive 6 single dose vials to be injected intradermal monthly x 3 followed by boosters at 6, 12, and 18 months in the same lymph node draining area (preferably the anterior thigh). Patients must begin vaccinations between 3 weeks and 3 months from completion of (SoC). Frozen tumor will be maintained for active vaccines for all patients to include the control patients. The latter will be offered their active vaccine at time of recurrence in a crossover fashion. Additionally, control patients who do not recur will be offered active vaccine at the completion of the trial.

Safety data will be collected on local and systemic toxicities and graded and reported per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Disease-free status will be monitored per SoC as outlined by NCCN. Suspected recurrences will be documented with biopsy and pathologic confirmation. Time to recurrence will be based on date of randomization to time of confirmed recurrence.

Recurrent patients will be offered participation in the open label portion of the study. New active vaccine will be made for all patients, and they will be inoculated at 0, 1, 2, 3, 6, and 9 mos. Patients will be treated per SoC for their recurrence. Safety and tumor response will be assessed per RECIST and irRC on their SoC follow-up scans.

Blood (50 mL) will be collected from all patients prior to each inoculation and at 24 months from enrollment for a total of 7 time points or a total of 350 mL of blood over 2 years. The collected blood will be sent to our central facility for immunologic testing of the T-cell response.

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • University of Alabama Birmingham (UAB) Comprehensive Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Cancer Clinical Research Office
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute A Cedars-Sinai Affiliate
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Cancer Research Program
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Northside Hospital Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Cancer Care Alliance
  • New York
    • New York, New York, United States, 10016
      • Laura and Isaac Permutter Cancer Center @ NYU Langone
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Institute
    • Columbus, Ohio, United States, 43202
      • The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • St. Francis Hospital Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/The University of Utah
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status 0,1 (Appendix D)
• AJCC stage III or IV completely resectable melanoma identified before surgery
• Approximately 1 mg (1 cm3) of accessible and dispensable tumor that will not interfere with pathologic staging
• Clinically disease-free after surgery
• Completing SoC adjuvant therapy per NCCN guidelines to include chemotherapy, radiation therapy, and/or biologic therapy as clinically indicated. (Consent #2 should be signed as close to completion of SoC as possible but may overlap completion by up to one month.)
• Vaccinations initiated between 3 weeks and 3 months from completion of SoC multi-modality cancer care
• Adequate organ function as determined by the following laboratory values:
• ANC ≥ 1,000/μL
• Platelets ≥ 75,000/μL
• Hgb ≥ 9 g/dL
• Creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance ≥ 50%
• Total bilirubin ≤ 1.5 ULN
• ALT and AST ≤ 1.5 ULN
• For women of child-bearing potential, agreement to use adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)
• Signed informed consent

Exclusion Criteria:

• Evidence of residual disease after surgery and SoC adjuvant therapies
• Insufficient tumor available to produce vaccine
• ECOG >2 performance status (Appendix D)
• Immune deficiency disease or known history of HIV, HBV, HCV
• Receiving immunosuppressive therapy including chronic steroids, methotrexate, or other known immunosuppressive agents
• Pregnancy (assessed by urine HCG)
• Breast feeding
• Active pulmonary disease requiring medication to include multiple inhalers (>2 inhalers and one containing steroids)
• Involved in other experimental protocols (except with permission of the other study PI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; autologous TLPLDC (active vaccine)	Drug: TLPLDC; Autologous tumor lysate, particle-loaded dendritic cell vaccine
Placebo Comparator: Placebo; unloaded YCWP + autologous DC (control)	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival Assessment	The primary outcome measure of the trial is assessing disease free survival (DFS) at 24 months compared between the vaccinated and control groups after the final enrolled patient completes two years of follow-up. An interim analysis will be performed six months after the final patient is enrolled. This analysis will compare median DFS between vaccinated and control groups.	24 months

Collaborators and Investigators

• Sponsor: Cancer Insight, LLC
• Collaborators: Elios Therapeutics, LLC
• Investigators: Study Director: George E Peoples, MD, LumaBridge

Publications and helpful links

General Publications

• Vreeland TJ, Clifton GT, Hale DF, Chick RC, Hickerson AT, Cindass JL, Adams AM, Bohan PMK, Andtbacka RHI, Berger AC, Jakub JW, Sussman JJ, Terando AM, Wagner T, Peoples GE, Faries MB. A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis. Ann Surg Oncol. 2021 Oct;28(11):6126-6137. doi: 10.1245/s10434-021-09709-1. Epub 2021 Feb 27.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): May 11, 2022
• Study Completion (Actual): May 11, 2022

Study Registration Dates

• First Submitted: November 12, 2014
• First Submitted That Met QC Criteria: November 23, 2014
• First Posted (Estimate): November 26, 2014

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 20141932