Topics

Chemotherapy Consisting of Fludarabine and Cyclophosphamide Followed By White Blood Cell Infusion, Vaccine Therapy, and Aldesleukin in Treating Patients With Recurrent or Refractory Metastatic Melanoma

2014-08-27 03:54:19 | BioPortfolio

Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Treated white blood cells, vaccines, and aldesleukin may make the body build an immune response to kill tumor cells.

PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with white blood cell infusion, vaccine therapy, and aldesleukin works in treating patients with recurrent or refractory metastatic melanoma.

Description

OBJECTIVES:

Primary

- Determine complete clinical tumor regression in patients with recurrent or refractory metastatic melanoma treated with lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising fludarabine and cyclophosphamide followed by autologous lymphocyte infusion, recombinant fowlpox virus encoding gp100 peptide, and aldesleukin.

Secondary

- Determine the survival of patients treated with this regimen.

- Determine the safety of this regimen in these patients.

OUTLINE: Patients are stratified according to the availability of suitable reactive cells (peripheral blood lymphocytes [PBL] vs tumor-infiltrating lymphocytes [TIL]).

- Autologous lymphocyte activation and expansion: Autologous PBL or TIL are activated in vitro with gp100:209-217 (210M) antigen (gp100) and expanded.

- Lymphocyte-depleting nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes on days -5 to -1.

- Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused over 20-30 minutes on day 0*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 or 2 and continuing until blood counts recover.

- Fowlpox vaccine administration: Patients receive recombinant fowlpox virus encoding gp100 peptide IV over 1-2 minutes on days 2 and 28 (if treated with high-dose aldesleukin [IL-2], as below) OR days 2 and 43 (if treated with low-dose IL-2, as below).

- IL-2 therapy: Patients receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0*-4 (beginning within 24 hours after lymphocyte infusion) and 28-32 OR low-dose IL-2 SC on days 0*-4 (beginning within 24 hours after lymphocyte infusion), 7-11, 14-18, 21-25, 28-32, 35-39, 50-54, 57-61, 64-68, 71-75, 78-82, and 85-89.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients are evaluated between days 72-86 (if treated with high-dose IL-2) OR days 98-123 (if treated with low-dose IL-2). Patients with stable disease or a minor, mixed, or partial response may receive up to 2 retreatment courses as above. Patients with progressive disease after IV lymphocyte infusion may be retreated with intra-arterial lymphocytes along with all other agents outlined above.

After completion of study treatment, patients are followed at 2-4 weeks (if treated with high-dose IL-2) OR at 3 weeks (if treated with low-dose IL-2) and then annually thereafter.

PROJECTED ACCRUAL: A total of 68 will be accrued for this study.

Study Design

Masking: Open Label, Primary Purpose: Treatment

Conditions

Melanoma (Skin)

Intervention

aldesleukin, filgrastim, fowlpox virus vaccine vector, gp100 antigen, therapeutic autologous lymphocytes, therapeutic tumor infiltrating lymphocytes, cyclophosphamide, fludarabine phosphate

Location

NCI - Surgery Branch
Bethesda
Maryland
United States
20892-1201

Status

Completed

Source

National Cancer Institute (NCI)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:54:19-0400

Clinical Trials [3910 Associated Clinical Trials listed on BioPortfolio]

Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether combining melanoma vaccine with interleukin-2 is more effective than vaccine...

Thai Prophylactic Vaccine Study

The development of a safe and effective vaccine for HIV is the subject of intensive world-wide research. Various approaches are being investigated in monkey models and humans. This is a ra...

Vaccine Therapy in Treating Patients With Metastatic Melanoma

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. PURPOSE: Randomized phase...

Vaccine Therapy and GM-CSF With or Without Low-Dose Aldesleukin in Treating Patients With Stage II, Stage III, or Stage IV Melanoma

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immu...

Vaccine Therapy in Treating Patients With Melanoma

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Vaccine therapy may be an effective treatment for melanoma. PURPOSE: Randomized phase II trial to study...

PubMed Articles [6934 Associated PubMed Articles listed on BioPortfolio]

Recombinant vector vaccine evolution.

Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the tra...

Fusion of pseudorabies virus glycoproteins to IgG Fc enhances protective immunity against pseudorabies virus.

Molecular adjuvants are vaccine delivery vehicle to increase specific antigens effectiveness. Herein, we concentrated on IgG Fc, an effective molecular adjuvant, to develop novel pseudorabies virus (P...

First-in-human randomized study to assess the safety and immunogenicity of an investigational respiratory syncytial virus (RSV) vaccine based on ChAd155 viral vector expressing RSV viral proteins F, N and M2-1 in healthy adults.

Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This phase I, randomized, observer-blind, placebo- and active-controlled study (NCT02491463) evaluated an ...

Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge.

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8+ T cel...

A chimpanzee adenoviral vector-based rabies vaccine protects beagle dogs from lethal rabies virus challenge.

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldw...

Medical and Biotech [MESH] Definitions

The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.

The type species of the genus AVIPOXVIRUS. It is the etiologic agent of FOWLPOX.

A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.

A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had mumps or been immunized with live mumps vaccine. Children are usually immunized with measles-mumps-rubella combination vaccine.

A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)

More From BioPortfolio on "Chemotherapy Consisting of Fludarabine and Cyclophosphamide Followed By White Blood Cell Infusion, Vaccine Therapy, and Aldesleukin in Treating Patients With Recurrent or Refractory Metastatic Melanoma"

Quick Search

Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one ...


Searches Linking to this Trial