Vaccination of Melanoma Patients With Total or CD25-depleted Peripheral Blood Mononuclear Cell (PBMC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Providence Health & Services.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Providence Health & Services
ClinicalTrials.gov Identifier:
NCT00961376
First received: August 14, 2009
Last updated: August 2, 2011
Last verified: July 2011
  Purpose

The objective of this study is to evaluate the safety and immunologic effects of autologous tumor vaccination administered with human granulocyte-macrophage colony-simulating factor (hGM-CSF), and subsequent boosting vaccinations in patients made lymphopenic by treatment with chemotherapy and infused with autologous PBMC (Cohort A) or CD25 depleted PBMC (Cohort B). Clinical observations and laboratory measurements will be monitored to evaluate safety, toxicity, immune responses, and anti-tumor effects. Additionally, the effects of treatment on tumor response will be evaluated.


Condition Intervention Phase
Melanoma
Biological: PBMC re-infusion
Biological: CD25 depletion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vaccination of Chemotherapy Induced Lymphopenic Unresectable Stage III or Stage IV Melanoma Patients Following Reconstitution With Total or CD25-depleted PBMC

Resource links provided by NLM:


Further study details as provided by Providence Health & Services:

Primary Outcome Measures:
  • Immunologic effects (changes in the number of tumor specific T cells) [ Time Frame: Up to day 119 ] [ Designated as safety issue: No ]
    The absolute number and frequency of tumor specific T cells will be measured at days 7, 21, 35, 64, 91, and day 119.


Secondary Outcome Measures:
  • The number and severity of adverse events [ Time Frame: Up to day 119 ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed on Days 7, 21, 35, 64, 91, and 119. Of special interest will be any adverse events thought to represent an autoimmune reaction.


Estimated Enrollment: 14
Study Start Date: July 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort A
PBMC re-infusion
Biological: PBMC re-infusion
Autologous PBMC re-infusion
Experimental: Cohort B
CD25 depletion
Biological: CD25 depletion
Autologous, CD25-depleted PBMC re-infusion

Detailed Description:

This is an open-label, outpatient Phase II, prospective, randomized, single-center, clinical trial. Up to 14 patients with a diagnosis of unresectable stage III or stage IV melanoma.

All patients will undergo leukapheresis to collect PBMC.

All patients will receive Cyclophosphamide 350 mg/m2 dl-3 and Fludarabine 20 mg/m2 dl-3.

Following chemotherapy to induce lymphopenia, patients will be re-infused with PDMC as follows:

Autologous PBMC re-infusion (Cohort A) Autologous, CD25-depleted PBMC re-infusion (Cohort B)

Following PBMC re-infusion, all patients will receive subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) continuously for 6 days.

All patients will then receive 4 booster vaccinations as follows:

Intradermal injection of autologous tumor cells in the lower abdomen to deliver a total dose of at least 2x107 cells administered week 3, week 5, week 9 and week 13. Subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) adjacent to the vaccine site begins at time of vaccination (week 3, 5, 9 and 13) and continues for 6 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed malignant melanoma that is unresectable stage III or stage IV. Measurable disease is not required.
  • Patients must have failed, refused, or not been eligible to receive at least one standard therapy regimen for metastatic disease.
  • Easily harvested metastatic tumor cells e.g., skin or lymph node metastases or a planned surgery to remove tumor. Patients undergoing resection of a solitary brain metastasis are eligible if their resected lesion contains an adequate number of tumor cells. A minimum 2 cm x 2 cm x 2 cm lesion will be required for study eligibility.
  • Sufficient viable tumor cells harvested to generate the vaccine. The tumor collected must contain greater than 1.6 x 108 viable tumor cells or a cell line generated from autologous tumor must provide greater than 1.6 x 108 viable tumor cells.
  • Patients may have received prior chemotherapy and/or immunotherapy. Prior radiation therapy is acceptable but previously radiated sites may not be used for tumor collection for vaccine preparation.
  • Life expectancy of greater than or = 3 months.
  • ECOG performance status <2 (Karnofsky >60%; see Appendix A).
  • Patients must have normal organ and marrow function at the time of enrollment as defined in the protocol.
  • Patients must be seronegative for HIV, Hepatitis B surface antigen and Hepatitis C antibody.
  • If patients have had recent surgery, they must have recovered from the effects of that surgery in the opinion of the investigator.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C).
  • Radiation therapy within 2 weeks. Prior radiation must have been to less 30% of the bone marrow and patient has recovered from all side effects, in the opinion of the investigator.
  • Patients may not be receiving any other investigational agents.
  • Steroid therapy, other than replacement steroids and inhaled steroids. Patients who might require systemic corticosteroids other than replacement steroids during the next three months are not eligible for this study.
  • Patients with known brain metastases unless treated with radiation therapy and/or surgery and shown to be stable > 1 month.
  • Autoimmune disease requiring treatment, with the exception of controlled autoimmune thyroiditis or vitiligo.
  • Pregnant or nursing women are excluded from this study because fludarabine and cyclophosphamide have potential teratogenic effects. It is not known whether fludarabine is excreted in breast milk but the package insert cautions that it might and recommends against breastfeeding if the mother is treated with fludarabine.
  • Uncontrolled intercurrent illness which, in the opinion of the investigator, may increase the risks associated with study participation or interfere with the interpretation of the results..
  • Any other medical illness or psychiatric condition/social situations that in the opinion of the principal investigator would compromise the patients ability to tolerate this treatment or would limit compliance with study requirements.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00961376

Contacts
Contact: Chris Fountain, RN 503-215-2691 christopher.fountain@providence.org

Locations
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Chris Fountain, RN    503-215-2691    christopher.fountain@providence.org   
Principal Investigator: Brendan Curti, MD         
Sponsors and Collaborators
Providence Health & Services
  More Information

No publications provided

Responsible Party: Bernard Fox, PhD, Providence Portland Medical Center
ClinicalTrials.gov Identifier: NCT00961376     History of Changes
Other Study ID Numbers: PHS IRB 06-55
Study First Received: August 14, 2009
Last Updated: August 2, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Providence Health & Services:
melanoma
unresectable stage III or IV melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 16, 2014