Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00062036
• Other study ID #: 030162
• Secondary ID: 03-C-0162NCI-585
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 5, 2003
• Last updated: June 30, 2017
• Start date: June 2003
• Est. completion date: September 2008

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Other known NCT identifiers

• NCT00059163

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: September 2008
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• aldesleukin

• filgrastim

• incomplete Freund's adjuvant

• interleukin-2 gene

• therapeutic tumor infiltrating lymphocytes

Drug:
• cyclophosphamide

• fludarabine phosphate

Locations

Country	Name	City	State
United States	NCI - Center for Cancer Research	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival
Secondary	Clinical tumor regression
Secondary	Toxicity profile