Phase IIB TL + YCWP + DC in Melanoma



Status:Recruiting
Conditions:Skin Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - 99
Updated:12/19/2018
Start Date:January 2015
End Date:June 2019
Contact:Katie Lyon, MS, CCRP
Email:klyon@cancerinsight.com
Phone:210-952-6301

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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.

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.

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)
We found this trial at
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Tucson, Arizona 85724
Principal Investigator: Montaser Shaheen, MD
Phone: 520-694-9057
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2200 Santa Monica Blvd
Santa Monica, California 90404
(310) 582-7438
Principal Investigator: Steven O'Day, MD
Phone: 310-582-7456
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Albuquerque, New Mexico 87109
Principal Investigator: Emrullah Yilmaz, MD
Phone: 505-925-0370
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Atlanta, Georgia 30341
Principal Investigator: Ronald Steis, MD
Phone: 770-496-9457
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Birmingham, Alabama 35294
Principal Investigator: Robert M Conry, MD
Phone: 205-978-2848
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251 E Huron St
Chicago, Illinois 60611
(312) 926-2000
Principal Investigator: Sunandana Chandra, MD
Phone: 312-695-1341
Northwestern Memorial Hospital Northwestern Memorial is an academic medical center hospital where the patient comes...
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Cincinnati, Ohio 45267
Principal Investigator: Jeffrey Sussman, MD
Phone: 513-584-0439
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Columbus, Ohio 43210
Principal Investigator: Doreen Agnese, MD
Phone: 614-366-5251
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20 Duke Clinic Cir
Durham, North Carolina 27710
(888) 275-3853
Principal Investigator: John Stewart, MD
Phone: 919-668-3771
Duke Cancer Institute Leading-edge cancer care and research have been a hallmark of Duke Medicine...
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Everett, Washington 98201
Principal Investigator: Perry Soriano, MD
Phone: 425-297-5531
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Greenville, South Carolina 29607
Principal Investigator: Robert Siegel, MD
Phone: 864-603-6222
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Laguna Hills, California 92653
Principal Investigator: Kenneth Deck, MD
Phone: 949-680-3490
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Los Angeles, California 90025
Principal Investigator: Mark Faries, MD
Phone: 310-582-7900
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4300 Alton Road
Miami Beach, Florida 33140
Principal Investigator: Jose Lutzky, MD
Phone: 305-674-2625
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New York, New York 10016
Principal Investigator: Anna Pavlick, MD
Phone: 212-263-4414
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1020 Walnut St
Philadelphia, Pennsylvania 19107
(215) 955-6000
Principal Investigator: Adam Berger, MD
Phone: 215-503-5388
Thomas Jefferson University We are dedicated to the health sciences and committed to educating professionals,...
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Phoenix, Arizona 85054
Principal Investigator: Nabil Wasif, MD
Phone: 480-342-6012
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200 First Street SW
Rochester, Minnesota 55905
507-284-2511
Principal Investigator: James Jakub, MD
Phone: 507-284-0602
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
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2000 Circle of Hope Dr
Salt Lake City, Utah 84112
(801) 585-0303
Principal Investigator: John Hyngstrom, MD
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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615 N Michigan St
South Bend, Indiana 46601
(574) 647-1000
Principal Investigator: Thomas Reid, III, MD
Phone: 574-647-3305
Memorial Hospital of South Bend Memorial Hospital of South Bend is a community-owned, not-for-profit corporation...
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