Phase IIB TL + YCWP + DC in Melanoma

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. Identifier: NCT02301611
Recruitment Status : Recruiting
First Posted : November 26, 2014
Last Update Posted : December 7, 2018
Elios Therapeutics, LLC
Information provided by (Responsible Party):
Cancer Insight, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: TLPLDC Drug: Placebo Phase 2

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  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : January 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Treatment
autologous TLPLDC (active vaccine)
Autologous tumor lysate, particle-loaded dendritic cell vaccine

Placebo Comparator: Placebo
unloaded YCWP + autologous DC (control)
Drug: Placebo

Primary Outcome Measures :
  1. Disease Free Survival Assessment [ Time Frame: 24 months ]
    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.

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.

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

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 identifier (NCT number): NCT02301611

Contact: Katie Lyon, MS, CCRP 210-952-6301
Contact: Sherri Thomas, RN, BSN, CCRP 210-844-5861

United States, Alabama
University of Alabama Birmingham (UAB) Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35243
Contact: Teresa Ross    205-978-2848   
Contact: Patty Bunch, RN   
Principal Investigator: Robert M Conry, MD         
United States, Arizona
Mayo Clinic - Cancer Clinical Research Office Recruiting
Phoenix, Arizona, United States, 85054
Contact: Eric Siebeneck    480-342-6012   
Contact: Jocelyn Cuevas    480-342-6012   
Principal Investigator: Nabil Wasif, MD         
Mayo Clínic-Cancer Clinical Research Office Recruiting
Phoenix, Arizona, United States, 85054
Contact: Eric Siebeneck   
Contact: Jocelyn Cuevas   
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Lisa Slayton    520-694-9057   
Contact: Cassandra Hall    520-694-1053   
Principal Investigator: Montaser Shaheen, MD         
United States, California
Alliance Research Centers Withdrawn
Laguna Hills, California, United States, 92653
The Angeles Clinic and Research Institute A Cedars-Sinai Affiliate Recruiting
Los Angeles, California, United States, 90025
Contact: Saba Mukarram    310-582-7900      
Principal Investigator: Mark Faries, MD         
John Wayne Cancer Institute Recruiting
Santa Monica, California, United States, 90404
Contact: Kelly Garver    310-582-7456   
Contact: Graham Toth    310-582-7421   
Principal Investigator: Steven O'Day, MD         
United States, Florida
Mount Sinai Cancer Research Program Recruiting
Miami Beach, Florida, United States, 33140
Contact: Yvonne Enriquez-Nunez    305-674-2625   
Principal Investigator: Jose Lutzky, MD         
United States, Georgia
Northside Hospital Cancer Institute Recruiting
Atlanta, Georgia, United States, 30341
Contact: Sally Haislip    770-496-9457   
Principal Investigator: Ronald Steis, MD         
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Sneha Solanki    312-695-1341   
Principal Investigator: Sunandana Chandra, MD         
Principal Investigator: Jeff Wayne, MD         
United States, Indiana
Memorial Hospital of South Bend Recruiting
South Bend, Indiana, United States, 46601
Contact: Pam Wasielewski, RN, BSN OSN    574-647-3305   
Principal Investigator: Thomas Reid, III, MD         
United States, New Mexico
New Mexico Cancer Care Alliance Recruiting
Albuquerque, New Mexico, United States, 87102
Contact: Olivia Reynolds    505-925-0370   
Contact: Terry Novak    505-925-0357   
Principal Investigator: Olivier Rixe, MD         
United States, New York
Laura and Isaac Permutter Cancer Center @ NYU Langone Recruiting
New York, New York, United States, 10016
Contact: Malcolm DeLara    212-263-4414   
Principal Investigator: Anna Pavlick, MD         
United States, North Carolina
Duke Cancer Institute Withdrawn
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati Cancer Institute Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Bree Kinne, RN    513-584-0439   
Principal Investigator: Jeffrey Sussman, MD         
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43202
Contact: Lauren Kulesza    614-366-5251   
Principal Investigator: Doreen Agnese, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Subikram Chanda    215-503-5388   
Principal Investigator: Adam Berger, MD         
United States, South Carolina
St. Francis Hospital Cancer Center Recruiting
Greenville, South Carolina, United States, 29607
Contact: Amber Lewis, BSN, RN    864-603-6222   
Principal Investigator: Robert Siegel, MD         
United States, Utah
Huntsman Cancer Institute/The University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Andrea Farmer, RN   
Principal Investigator: John Hyngstrom, MD         
United States, Washington
Providence Regional Medical Center Everett Recruiting
Everett, Washington, United States, 98201
Contact: Kathleen Butler, BA, CCRC    425-297-5577   
Principal Investigator: Perry Soriano, MD         
Sponsors and Collaborators
Cancer Insight, LLC
Elios Therapeutics, LLC
Study Director: George E Peoples, MD Cancer Insight, LLC

Responsible Party: Cancer Insight, LLC Identifier: NCT02301611     History of Changes
Other Study ID Numbers: WIRB Protocol: 20141932
First Posted: November 26, 2014    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Immunologic Factors
Physiological Effects of Drugs