Cyclophosphamide and Fludarabine Followed by Vaccine Therapy, Gene-Modified White Blood Cell Infusions, and Aldesleukin in Treating Patients With Metastatic Melanoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00091104
First received: September 7, 2004
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.


Condition Intervention Phase
Melanoma (Skin)
Biological: MART-1:27-35 peptide vaccine
Biological: aldesleukin
Biological: filgrastim
Biological: incomplete Freund's adjuvant
Biological: therapeutic autologous lymphocytes
Biological: therapeutic tumor infiltrating lymphocytes
Drug: cyclophosphamide
Drug: fludarabine phosphate
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Tumor regression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • In vivo survival of transplanted cells [ Designated as safety issue: No ]
  • Clinical response [ Designated as safety issue: No ]

Estimated Enrollment: 136
Study Start Date: July 2004
Study Completion Date: October 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of metastatic melanoma
  • HLA-A*0201-positive disease
  • Measurable disease
  • Refractory to standard therapy, including high-dose aldesleukin therapy

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 8.0 g/dL
  • Lymphocyte count > 500/mm^3
  • WBC > 3,000/mm^3
  • No coagulation disorder

Hepatic

  • ALT and AST < 3 times upper limit of normal
  • Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL for patients with Gilbert's disease)
  • Hepatitis B antigen negative
  • Hepatitis C antibody negative (unless antigen negative)

Renal

  • Creatinine ≤ 1.6 mg/dL

Cardiovascular

  • No myocardial infarction
  • No cardiac arrhythmias
  • No cardiac ischemia
  • LVEF ≥ 45% by stress cardiac test* (for patients ≥ 50 years of age OR those with a history of EKG abnormalities)
  • No other major cardiovascular illness by stress thallium or comparable test NOTE: *Stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test

Pulmonary

  • No major respiratory illness
  • No obstructive or restrictive pulmonary disease
  • FEV_1 ≥ 60% of predicted on pulmonary function test*
  • DLCO ≥ 60% predicted (for total-body irradiation cohort) NOTE: *For patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction

Immunologic

  • HIV negative
  • No major immune system illness
  • No active systemic infection or opportunistic infection
  • No primary immunodeficiency (e.g., autoimmune colitis or Crohn's disease)
  • No secondary immunodeficiency (e.g., due to chemotherapy or radiotherapy)
  • No history of severe immediate hypersensitivity reaction to study drugs

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after completion of study treatment
  • Must sign a durable power of attorney

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • Recovered from prior immunotherapy
  • Prior immunization to melanoma antigens allowed

    • Progressive disease during prior immunization allowed
  • Prior cellular therapy, including vector transduction with or without myeloablation, allowed
  • More than 6 weeks since prior anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibody (MDX-010) therapy
  • No prior anti-CTLA-4 antibody unless a post anti-CTLA-4 antibody treatment colonoscopy was normal by biopsy

Chemotherapy

  • Recovered from prior chemotherapy

Endocrine therapy

  • No concurrent systemic steroids

Radiotherapy

  • Recovered from prior radiotherapy
  • No prior significant mediastinal or lung radiation (for total-body irradiation cohort)

Surgery

  • Not specified

Other

  • More than 4 weeks since prior systemic therapy and recovered
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091104

Locations
United States, Maryland
NCI - Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00091104     History of Changes
Obsolete Identifiers: NCT00088439
Other Study ID Numbers: 040251, 04-C-0251, NCI-6974, CDR0000383246
Study First Received: September 7, 2004
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
stage IV melanoma
recurrent 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
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Freund's Adjuvant
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on July 24, 2014