Clinical trial · Interventional
Anti-gp100 Cells Plus ALVAC gp100 Vaccine to Treat Advanced Melanoma
Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 TCR-Gene Engineered Lymphocytes and ALVAC Virus Immunization
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The study was terminated due to low accrual.
Summary
Brief summary (as posted)
Background: * gp100 is a protein that is often found in melanoma tumors. * An experimental procedure developed for treating patients with melanoma uses anti-gp100 cells designed to destroy their tumors. The anti-gp100 cells are created in the laboratory using the patient's own tumor cells or blood cells. * The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) gp100, made from a virus that ordinarily infects canaries and is modified to carry a copy of the gp100 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti gp 100 cells. Objectives: -To evaluate the safety and effectiveness of anti-gp100 cells and the ALVAC gp100 vaccine in treating patients with advanced melanoma. Eligibility: -Patients with metastatic melanoma for whom standard treatments have not been effective. Design: * Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment. * Patients have 7 days of chemotherapy to prepare the immune system for receiving the gp100 cells. * Patients receive the ALVAC vaccine, anti-gp100 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti gp100 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of gp100 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses. * After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Melanoma | Melanoma | CURATED_BROADER | 0.78 |
| Skin Cancer | Malignant Skin Neoplasm | ALIAS | 0.90 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Aldesleukin | Biological | Aldesleukin | ALIAS |
| ALVAC gp100 Vaccine | Biological | — | UNRESOLVED |
| anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL) | Biological | — | UNRESOLVED |
| cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| fludarabine phosphate | Drug | Fludarabine | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
- description
- ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10\^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10\^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2mL. This will be repeated on day 14. Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
- interventionNames
- Drug: cyclophosphamide
- Drug: fludarabine phosphate
- Biological: Aldesleukin
- Biological: ALVAC gp100 Vaccine
- Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
Primary outcomes (1)
- measure
- Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR)
- timeFrame
- 4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
-INCLUSION CRITERIA:
1. Metastatic melanoma with measurable disease.
2. Previously received high dose interleukin-2 (IL-2) and have been either non-responders (progressive disease) or have recurred.
3. Positive for gp100 by immunohistochemistry (IHC) which will be reviewed by the Laboratory of Pathology at National Cancer Institute (NCI).
4. Tumor infiltrating lymphocyte (TIL) cells not available for treatment on other Surgery Branch protocols.
5. Greater than or equal to 18 years of age.
6. Willing to sign a durable power of attorney.
7. Able to understand and sign the Informed Consent Document.
8. Clinical performance status of Eastern Oncology Oncology Group (ECOG) 0 or 1.
9. Life expectancy of greater than three months.
10. Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
11. Must be human leukocyte antigens (HLA-A) 0201 positive.
12. Serology:
* Seronegative for human immunodeficiency virus (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.)
* Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
13. Hematology:
* Absolute neutrophil count greater than 1000/mm\^3.
* White blood cell (WBC) (greater than 3000/mm\^3).
* Platelet count greater than 100,000/mm\^3.
* Hemoglobin greater than 8.0 g/dl.
14. Chemistry
* Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal.
* Serum creatinine less than or equal to 1.6 mg/dl.
* Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
15. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
16. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
17. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to decline, and patients who have previously received MDX-010 or ticilimumab must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA:
1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
2. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
4. Ongoing opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
5. Systemic steroid therapy.
6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
7. History of coronary revascularization.
8. Documented left ventricular ejection fraction (LVEF) of less than 45 percent in patients with:
* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2 degree or 3 degree heart block.
* Age greater than or equal to 60 years old.
9. Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60 percent predicted for patients with:
* A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years).
* Symptoms of respiratory distress.References
Publications (3)
- BACKGROUNDKawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9. doi: 10.1073/pnas.91.9.3515. PMID 8170938
- BACKGROUNDKawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347. PMID 7516411
- BACKGROUNDWalter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44. doi: 10.1056/NEJM199510193331603. PMID 7675046