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

Primary Purpose

Melanoma (Skin)

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tumor Infiltrating Lymphocytes (TIL)

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage IV melanoma, recurrent melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Aurora St. Luke's Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Determine toxicity of treatment regimen.

Arm Description

Outcomes

Primary Outcome Measures

Primary Objective

Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.

Secondary Outcome Measures

Full Information

NCT ID

NCT00863330

First Posted

March 17, 2009

Last Updated

December 16, 2014

Sponsor

Aurora Health Care

1. Study Identification

Unique Protocol Identification Number

NCT00863330

Brief Title

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

Official Title

A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Terminated

Why Stopped

administrative decision- PI retired and treating physician left the institution

Study Start Date

February 2009 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Aurora Health Care

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma (Skin)

Keywords

stage IV melanoma, recurrent melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Determine toxicity of treatment regimen.

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Tumor Infiltrating Lymphocytes (TIL)

Intervention Description

Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.

Primary Outcome Measure Information:

Title

Primary Objective

Description

Time Frame

4-6 weeks after completion of TIL

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John P. Hanson, MD

Organizational Affiliation

St. Luke's Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jonathan S. Treisman, MD

Organizational Affiliation

St. Luke's Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aurora St. Luke's Medical Center

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53215

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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