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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02301611
Recruitment Status : Active, not recruiting
First Posted : November 26, 2014
Last Update Posted : December 23, 2019
Sponsor:
Collaborator:
Elios Therapeutics, LLC
Information provided by (Responsible Party):
Cancer Insight, LLC

Tracking Information
First Submitted Date  ICMJE November 12, 2014
First Posted Date  ICMJE November 26, 2014
Last Update Posted Date December 23, 2019
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIB TL + YCWP + DC in Melanoma
Official Title  ICMJE 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.
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: TLPLDC
    Autologous tumor lysate, particle-loaded dendritic cell vaccine
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Treatment
    autologous TLPLDC (active vaccine)
    Intervention: Drug: TLPLDC
  • Placebo Comparator: Placebo
    unloaded YCWP + autologous DC (control)
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 7, 2019)
184
Original Estimated Enrollment  ICMJE
 (submitted: November 23, 2014)
120
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02301611
Other Study ID Numbers  ICMJE WIRB Protocol: 20141932
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cancer Insight, LLC
Study Sponsor  ICMJE Cancer Insight, LLC
Collaborators  ICMJE Elios Therapeutics, LLC
Investigators  ICMJE
Study Director: George E Peoples, MD Cancer Insight, LLC
PRS Account Cancer Insight, LLC
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP