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

• Sponsor: Aurora Health Care (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00863330
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 40.9
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: Tumor Infiltrating Lymphocytes (TIL)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Determine toxicity of treatment regimen.	Biological: Tumor Infiltrating Lymphocytes (TIL); Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.

Outcome Measures

Primary Outcome Measures

1. Primary Objective [4-6 weeks after completion of TIL]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Aurora Health Care

Investigators

• Principal Investigator: John P. Hanson, MD, St. Luke's Medical Center
• Principal Investigator: Jonathan S. Treisman, MD, St. Luke's Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jackie Blundon, MS, CIP, Research Regulatory Specialist, Aurora Health Care
• ClinicalTrials.gov Identifier: NCT00863330
• Other Study ID Numbers: CDR0000636885; STLMC-L-0839
• First Posted: Mar 18, 2009
• Last Update Posted: Jan 6, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Jackie Blundon, MS, CIP, Research Regulatory Specialist, Aurora Health Care: stage IV melanoma; recurrent melanoma
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Pre-assignment Detail	14 participants were enrolled. For those, 8 were screen failures and 6 started the study.

Arm/Group Title	Determine Toxicity of Treatment Regimen.
Arm/Group Description	Tumor Infiltrating Lymphocytes (TIL): Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
Period Title: Overall Study
STARTED	6
COMPLETED	0
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Determine Toxicity of Treatment Regimen.
Arm/Group Description	Tumor Infiltrating Lymphocytes (TIL): Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
Overall Participants	6
Age, Customized (participants) [Number]
18 or over	6 100%
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Primary Objective
Description	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.
Time Frame	4-6 weeks after completion of TIL

Outcome Measure Data

Analysis Population Description

Study was terminated for administrative reasons. complete data was not collected and no data analysis was completed

Arm/Group Title	Determine Toxicity of Treatment Regimen.
Arm/Group Description	Tumor Infiltrating Lymphocytes (TIL): Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
Measure Participants	0

Adverse Events

Arm/Group Title	Determine Toxicity of Treatment Regimen.
Arm/Group Description	Tumor Infiltrating Lymphocytes (TIL): Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
All Cause Mortality
	Determine Toxicity of Treatment Regimen.
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Determine Toxicity of Treatment Regimen.
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Determine Toxicity of Treatment Regimen.
	Affected / at Risk (%)	# Events
Total	0/6 (0%)

Limitations/Caveats

Study was ended early, before substantial data could be collected, due to Investigators retiring/leaving the institution.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.