Tumor Infiltrating Lymphocytes and Aldesleukin after Chemotherapy in Treating Patients with Metastatic Cancers

  • Resize font
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IITreatment18 and over10-C-0166
NCI-2013-01461, 100166, P09567, NCT01174121

Trial Description

Summary

This phase II trial studies how well tumor infiltrating lymphocytes and aldesleukin work after chemotherapy in treating patients with cancers that has spread to other parts of the body (metastatic). Aldesleukin may stimulate lymphocytes to kill tumor cells. Treating lymphocytes with aldesleukin in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body after chemotherapy.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine the rate of tumor regression in patients with metastatic digestive tract cancers who receive autologous, minimally cultured, cluster of differentiation 8 (CD8)+ enriched tumor infiltrating lymphocytes (TIL) plus aldesleukin following a lymphodepleting preparative regimen.

II. To determine the rate of tumor regression in patients in cohort 2 with metastatic digestive tract cancers who receive autologous, minimally cultured tumor infiltrating lymphocytes (TIL) plus aldesleukin following a lymphodepleting preparative regimen.

III. To determine the rate of tumor regression in patients in cohort 2 with metastatic digestive tract and urothelial cancers who receive autologous, minimally cultured tumor infiltrating lymphocytes (TIL) plus aldesleukin following a lymphodepleting preparative regimen.

IV. To determine the rate of tumor regression in patients in cohort 2 with metastatic digestive tract, urothelial, breast, and ovarian/endometrial cancers who receive autologous, minimally cultured tumor infiltrating lymphocytes (TIL) plus aldesleukin following a lymphodepleting preparative regimen.

SECONDARY OBJECTIVES:

I. To determine the phenotypic and functional characteristics of TIL derived from digestive tract, urothelial, breast, and ovarian/endometrial cancers.

II. To determine the toxicity of this treatment regimen.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.

TIL INFUSION: Patients receive autologous TIL IV over 20-30 minutes on day 0.

ALDESLEUKIN: Beginning within 24 hours of cell infusion, patients receive aldesleukin IV over 15 minutes every 8-24 hours on days 0-4. Patients also receive filgrastim subcutaneously (SC) on days 1-4 or until absolute neutrophil count begins to return to normal.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4-6 weeks, at 12 weeks, every 3 months for 9 months, every 6 months for 1 year, and then periodically thereafter.

Eligibility Criteria

Inclusion Criteria:

All patients must be refractory to approved standard systemic therapy; specifically:

Metastatic colorectal patients must have received oxaliplatin or irinotecan

Hepatocellular carcinoma patients must have received sorafenib (Nexavar®) since level 1 data support a survival benefit with this agent

Breast and ovarian cancer patients must be refractory to both 1st line and 2nd line treatments and must have received at least one second line chemotherapy regimen

Measurable metastatic (stage IV) gastric, gastroesophageal, pancreatic, hepatocellular carcinoma, cholangiocarcinoma, gallbladder, colorectal, urothelial, breast, and ovarian/endometrial carcinomas with at least one lesion that is resectable for TIL generation with minimal morbidity preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit, plus one other lesion that can be measured

Six weeks must have elapsed since any prior anti-vascular endothelial growth factor (VEGF) or anti-tyrosine kinase receptors (TKR) therapy to allow antibody levels to decline

More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients’ toxicities must have recovered to a grade 1 or less; patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified

Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert’s syndrome, who must have a total bilirubin less than or equal to 3 mg/dl

Serum creatinine less than or equal to 1.6 mg/dl

Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than five times the upper limit of normal

Seronegative for active hepatitis B, and seronegative for hepatitis C antibody; if hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcriptase-polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative

Seronegative for human immunodeficiency virus (HIV) antibody

Normal prothrombin time (less than or equal to 15.2 seconds)

Platelet count greater than 100,000/mm^3

Hemoglobin greater than 8.0 g/dl; subjects may be transfused to reach this cut-off

Normal white blood cell (WBC) (> 3000/mm^3)

Absolute neutrophil count greater than 1000/mm^3 without support of filgrastim

Able to understand and sign the informed consent document

Willing to sign a durable power of attorney

Willing to practice birth control during treatment and for four months after receiving the treatment

Life expectancy of greater than three months

Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1

Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible

Exclusion Criteria:

Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction

Documented LVEF of less than or equal to 45% tested in patients with:

Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block

Age >= 60 years old

Any patient known to have a left ventricular ejection fraction (LVEF) less than or equal to 45%

History of coronary revascularization or ischemic symptoms

History of severe immediate hypersensitivity reaction to any of the agents used in this study

Concurrent opportunistic infections

Any form of primary immunodeficiency (such as severe combined immunodeficiency disease and acquired immune deficiency syndrome [AIDS])

Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion

Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease

Systemic steroid therapy required

Women of child-bearing potential who are pregnant or breastfeeding

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NCI - Center for Cancer Research

  • National Cancer Institute
Steven A. Rosenberg, Principal Investigator

Trial Sites

U.S.A.

Maryland
Bethesda

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Steven A. Rosenberg
Ph: 301-496-4164
Email: SAR@nih.gov

Steven A. Rosenberg
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01174121

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.