Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes 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:
NCT00062036
First received: June 5, 2003
Last updated: July 11, 2012
Last verified: March 2012
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Purpose
RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase I is closed to accrual 3/29/06).
| Condition | Intervention | Phase |
|---|---|---|
|
Melanoma (Skin) |
Biological: aldesleukin Biological: filgrastim Biological: incomplete Freund's adjuvant Biological: interleukin-2 gene Biological: therapeutic tumor infiltrating lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma |
Resource links provided by NLM:
Drug Information available for:
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Aldesleukin
Filgrastim
Lenograstim
Granulocyte colony-stimulating factor
U.S. FDA Resources
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Survival [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Clinical tumor regression [ Designated as safety issue: No ]
- Toxicity profile [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 33 |
| Study Start Date: | June 2003 |
| Study Completion Date: | September 2008 |
| Primary Completion Date: | February 2007 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- Determine the survival of patients with metastatic melanoma administered interleukin-2 gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine.
- Compare survival results with prior Surgery Branch studies using adoptive cell therapy without the interleukin-2 retroviral vector (SBIL-2) gene.
Secondary
- Determine clinical tumor regression in patients administered interleukin-2 gene-modified TIL after cyclophosphamide and fludarabine followed by interleukin-2.
- Determine the toxicity profile of this regimen in these patients.
OUTLINE:
Phase I (closed to accrual as of 3/29/06):
- Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over a period of approximately 4 weeks.
- Nonmyeloablative preparative regimen (chemotherapy): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30 minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, , until blood counts recover.
Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on disease status after each regimen. Patients with dose-limiting toxicity do not receive further treatment.
- No response: Patients with stable disease or disease progression after the initial treatment are followed or removed from the study.
- Partial response: Patients with a partial or minor response after the initial treatment may receive retreatment, approximately 2-4 weeks later, with chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as above, every 4-6 weeks for up to 2 courses provided at least a partial response is documented after each regimen.
- Complete response: Patients with a complete response receive no further treatment.
- Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2 gene-transduced TIL.
Patients are followed every 3-6 weeks in the absence disease progression.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Diagnosis of melanoma
- Metastatic disease
- Refractory to standard therapy including high-dose interleukin-2 (IL-2) therapy
- Evaluable disease
- Patients may enroll at the cell infusion stage provided they have tumor available for biopsy OR expandable SBIL-2-transduced tumor infiltrating lymphocytes available
- Progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed
- Symptomatic CNS lesions allowed provided immediate active treatment for symptomatic lesions has been completed
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count greater than 1,000/mm^3
- WBC greater than 3,000/mm^3
- Lymphocyte count greater than 500/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin greater than 8.0 g/dL
- No coagulation disorder
Hepatic
- Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome)
- AST/ALT less than 3 times upper limit of normal
- Hepatitis B surface antigen negative
- Hepatitis C virus negative
Renal
- Creatinine no greater than 1.6 mg/dL
Cardiovascular
- No myocardial infarction
- No cardiac arrhythmias
- No abnormal stress thallium or comparable test
LVEF > 45% and normal stress cardiac test in patients with the following criteria:
- 50 years old or greater
- History of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias
- No major cardiovascular illness
Pulmonary
- No obstructive or restrictive pulmonary disease
- No major respiratory illness
- FEV_1 > 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction
Immunologic
- HIV negative
- No prior severe immediate hypersensitivity reaction
- No primary or secondary immunodeficiency
- No active systemic infection
- No concurrent opportunistic infection
- No major immune system illness
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 months after study therapy
- Must sign a durable power of attorney
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior anti-cytotoxic T-lymphocyte antibody-4 antibody (CTLA-4) allowed unless post-MDX010 treatment and colonoscopy with colonic biopsies are normal
Chemotherapy
- Recovered from prior chemotherapy
Endocrine therapy
- No concurrent steroids
Radiotherapy
- Recovered from prior radiotherapy
Surgery
- Not specified
Other
- More than 4 weeks since prior systemic therapy
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00062036
Locations
| United States, Maryland | |
| NCI - Center for Cancer Research | |
| Bethesda, Maryland, United States, 20892 | |
| 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
| Responsible Party: | Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health |
| ClinicalTrials.gov Identifier: | NCT00062036 History of Changes |
| Obsolete Identifiers: | NCT00059163 |
| Other Study ID Numbers: | 030162, 03-C-0162, NCI-5855, CDR0000304438 |
| Study First Received: | June 5, 2003 |
| Last Updated: | July 11, 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 Interleukin-2 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 Analgesics, Non-Narcotic Analgesics |
ClinicalTrials.gov processed this record on May 21, 2013