Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma

Wake Forest University (WFU)

Status and phase

Terminated

Phase 2

Conditions

Melanoma (Skin)

Treatments

Biological: Tumor Infiltrating Lymphocytes (TIL)

Study type

Interventional

Funder types

Other

Identifiers

NCT00863330

CDR0000636885

STLMC-L-0839

Details and patient eligibility

About

RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated lymphocytes and aldesleukin together with cyclophosphamide and fludarabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma.

Full description

OBJECTIVES:

Primary

Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma.
Determine the toxicity of this treatment regimen.

Secondary

Determine the rate of repopulation of the young TIL cells.
Establish in vitro immunological correlates that predict in vivo persistence and clinical response.

OUTLINE:

Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.

Patients with stable disease, partial response, or recurrent disease after initial response may receive 1 additional course of treatment (as above) beginning 8 weeks after completion of aldesleukin.

Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then periodically thereafter for research studies. Samples are analyzed for differences in function and phenotype prior to and after TIL infusion. The immunological correlates of treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to determine cell phenotype and function; correlation of in vitro characteristics of the infused cells with in vivo antitumor activity; and the activity, specificity, and telomere length using flow FISH.

After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

Enrollment

14 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of metastatic melanoma
Refractory to standard treatment including high-dose aldesleukin (IL-2), unless previously ineligible for or refused IL-2
Measurable disease with ≥ 1 lesion that is resectable for tumor-infiltrating lymphocyte generation
Patients with ≥ 1 brain metastases < 1 cm each, or 1-2 brain metastases > 1 cm are eligible provided they have been treated and stable for ≥ 3 months

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy > 3 months
ANC > 1,000/mm^3 (without filgrastim support)
WBC > 3,000/mm^3
Hemoglobin > 8.0 g/dL
Platelet count > 100,000/mm^3
Serum ALT/AST < 3 times upper limit of normal
Total bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)
Serum creatinine ≤ 1.6 mg/dL
LVEF > 45% in patients meeting the following criteria:
- Clinically significant atrial and/or ventricular arrhythmias, including, but not limited to, atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block
- At least 60 years of age
FEV_1 > 60% in patients meeting the following criteria:
- Prolonged history of cigarette smoking
- Symptoms of respiratory dysfunction
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 months after completion of study treatment
No HIV or hepatitis B or C positivity
No form of primary immunodeficiency (e.g., severe combined immunodeficiency disease or AIDS)
No opportunistic infections
No active systemic infections
No history of severe immediate hypersensitivity reaction to any of the agents used in this study
No coagulation disorders
No myocardial infarction, cardiac arrhythmias, or positive stress thallium or comparable test
No history of coronary revascularization or ischemic symptoms
No obstructive or restrictive pulmonary disease
No other active major medical illness of the cardiovascular, respiratory, or immune system

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior therapy (alopecia or vitiligo allowed)
At least 6 weeks since prior ipilimumab
- Must have normal colonoscopy with normal colonic biopsies
At least 4 weeks since prior systemic therapy
Minor surgical procedures within the past 3 weeks allowed provided all toxicities have recovered to ≤ grade 1
No concurrent systemic steroids
No other concurrent experimental agents