Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Phase IIB TL + YCWP + DC in Melanoma

Protocol: OSU-14184

Full 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 in stage III and stage IV (resected) melanoma to prevent recurrence

Purpose

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 Objective

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 (approximately 1mg) of their melanoma sterilely frozen in the

operating room 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-α) and/or radiation therapy, then the vaccinations will not begin until SoC therapy

is completed. Once SoC therapies are complete and the patient deemed clinically

disease-free, they will be consented for treatment and randomized. Once consented, 120 mL of

blood will be collected from the patient and sent to our central facility for DC isolation

and preparation. 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 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.

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.

Are you eligible?

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)

Melanoma Skin Cancers