Melanoma Vaccine With Peptides and Leuprolide

NCT00254397 | Completed Phase 2 Results DMC

• 1 other identifier: 2004-0502
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the drug leuprolide will increase the level of immune cells in your body. Researchers will also want to know if this drug given together with melanoma vaccines (gp100 and MAGE-3) can improve the ability of tumor fighting immune cells (T cells) to fight melanoma cells. Primary Objective: 1\. To compare the tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of a luteinizing hormone-releasing hormone (LHRH) agonist-Leuprolide, in patients with stage IIb and III melanoma, uveal melanoma or stage IV melanoma that the metastatic lesion(s) has been surgically removed. Secondary Objectives:

1. 1.To evaluate the kinetics of enhanced thymic activity measured by TREC analysis and flow cytometric analysis following sex hormone ablation by Leuprolide in melanoma patients.
2. 2.To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide.

Conditions

Melanoma

Keywords

Melanoma; Uveal Melanoma; Peptide Vaccine; LHRH-agonist; Leuprolide; Lupron; MAGE-3 Peptide; MAGE-3; GP100 Peptide; Melanoma vaccines; Tumor fighting immune cells; T cells; Skin Cancer; Eye Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With T-cell Response to Peptide Vaccine

  Reactivity to the gp100 peptide in each participant defined as \>10 tetramer positive cells per 10\^4 CD8+ T-cells as determined by the tetramer analysis at 3 months following initial vaccine. Number of participants with response as defined reported. The primary end point of this clinical study was the comparison of tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of Leuprolide. Gp209-2M/HLA-A\*0201 tetramers that are commercially available employed to analyze levels of gp209-2M specific CD8+ cytolytic T cells. The levels of peptide/ HLA-A\*0201 tetramer between participants' peripheral blood mononuclear cells (PBMCs) with Leuprolide injection and without Leuprolide injection compared.

  At 3 months following initial vaccine.

Secondary Outcomes (3)

• Most Frequent and Most Serious Participant Adverse Events During Vaccine Treatment for Overall Study

  Baseline up to 48 weeks during vaccine treatment

• Number of Participants Experiencing Adverse Events by Maximum Grade Within Different Arms

  Baseline up to 48 weeks during vaccine treatment

• Summary of Adverse Events by Grade/Relationship

  Baseline up to 48 weeks during vaccine treatment

Study Arms (4)

gp100 + Leuprolide

EXPERIMENTAL

Group IA: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Drug: Leuprolide; Biological: GP100: 209-217(210M) Peptide

gp100 - No Leuprolide

EXPERIMENTAL

Group IB: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

Biological: GP100: 209-217(210M) Peptide

gp100 + MAGE-3 + Leuprolide

EXPERIMENTAL

Group IIA: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Drug: Leuprolide; Biological: GP100: 209-217(210M) Peptide; Biological: MAGE-3 Peptide

gp100 + MAGE-3 - No Leuprolide

EXPERIMENTAL

Group IIB: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

Biological: GP100: 209-217(210M) Peptide; Biological: MAGE-3 Peptide

Interventions

Leuprolide DRUG

A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).

Also known as: Lupron Depot, Lupron

gp100 + Leuprolide; gp100 + MAGE-3 + Leuprolide

GP100: 209-217(210M) Peptide BIOLOGICAL

1.0 ml subcutaneous injection in extremities.

gp100 + Leuprolide; gp100 + MAGE-3 + Leuprolide; gp100 + MAGE-3 - No Leuprolide; gp100 - No Leuprolide

MAGE-3 Peptide BIOLOGICAL

1.0 ml subcutaneous injection in extremities.

Also known as: MAGE-3

gp100 + MAGE-3 + Leuprolide; gp100 + MAGE-3 - No Leuprolide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HLA-A \*0201 positive
• Patients \>/= 18 years old with histologically documented diagnosis of stage IIb-IV melanomas and are clinically rendered free of disease after surgery
• Uveal melanoma patients following definitive treatment of radiation therapy and/or enucleation.
• Karnofsky Performance Scale \>/= 60%.
• White Blood Count (WBC) \>/= 3000/mm\^3.
• Platelet count \>/= 90,000mm\^3.
• Serum creatinine \</= 2.0mg/dl.
• Serum alanine aminotransferase (ALT) \</= 3 times upper limit of normal(ULN))
• Total bilirubin equal or less than 2 times upper limit of normal (ULN)), except for patient with Gilbert's syndrome who must have a total bilirubin less than 3.0mg/dl.
• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
• Negative pregnancy test by serum or urine b-HCG test for women who have menstruation in the past 12 months and without sterilization surgery.
• Unless surgically sterile by bilateral tubal-ligation or vasectomy of partner(s), the subject agrees to continue to use a barrier method of contraception throughout the study such as: condom, or diaphragm, or sponge plus spermicide. Abstinence is an acceptable form of birth control.

You may not qualify if:

• Prior systemic therapy (including immunomodulate agents), radiation or surgery requiring general anesthesia for melanoma within 28 days of starting study treatment.
• Autoimmune diseases.
• Concurrent systemic or inhaled steroid therapy.
• Any form of active primary or secondary immunodeficiency.
• History of immunization with gp100 or MAGE-3.
• Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated Stage I or II cancer from which the patient is currently in complete remission (at least for 5 years), or any other cancer from which the patient has been disease-free for 5 years.
• Received a Luteinizing hormone-releasing hormone (LHRH) agonist within the past 5 years.
• Use of oral contraceptive, hormone replacement therapy or androgen preparations.
• Hypersensitivity to gonadotropin-releasing hormone analogues.
• Active systemic infections requiring intravenous antibiotics.
• Lactating women or women planning lactation during the study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Melanoma; Uveal Melanoma; Skin Neoplasms; Eye Neoplasms

Interventions

Leuprolide; Peptides; MAGEA3 protein, human

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Patrick Hwu, MD / Professor, Melanoma Medical Oncology
• Organization: University of Texas MD Anderson Cancer Center

phwu@mdanderson.org

713-792-2921

Study Officials

• Patrick Hwu, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2005
• First Posted: November 16, 2005
• Study Start: November 1, 2005
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 16, 2019
• Results First Posted: October 16, 2019

Record last verified: 2019-09

Locations

US (1)