Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Colorectal Cancer; Metastatic Gastric Cancer; Metastatic Pancreatic Cancer; Metastatic Hepatocellular Carcinoma; Metastatic Cholangiocarcinoma
Intervention: Young TIL (Biological); Aldesleukin (Drug); Cyclophosphamide (Drug); Fludarabine (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: National Cancer Institute (NCI) Official(s) and/or principal investigator(s): Steven A Rosenberg, M.D., Principal Investigator, Affiliation: National Cancer Institute (NCI)
Overall contact: Jessica G Yingling, R.N., Phone: (866) 820-4505, Email: ncisbirc@mail.nih.gov
Summary
Background:
The NCI Surgery Branch has developed an experimental therapy that involves taking white
blood cells from patients' tumors, growing them in the laboratory in large numbers, and then
giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes,
or TIL and we have given this type of treatment to over 200 patients with melanoma.
Researchers want to know if TIL shrink s tumors in people with digestive tract,
urothelial, breast, or ovarian/endometrial cancers. In this study, we are selecting a
specific subset of white blood cells from the tumor that we think are the most effective in
fighting tumors and will use only these cells in making the tumor fighting cells.
Objective:
The purpose of this study is to see if these specifically selected tumor fighting cells can
cause digestive tract, urothelial, breast, or ovarian/endometrial tumors to shrink and to
see if this treatment is safe.
Eligibility:
- Adults age 18-70 with metastatic digestive tract, urothelial, breast, or
ovarian/endometrial cancer who have a tumor that can be safely removed.
Design:
Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo
a history and physical examination, scans, x-rays, lab tests, and other tests as needed.
Surgery: If the patients meet all of the requirements for the study they will undergo
surgery to remove a tumor that can be used to grow the TIL product.
Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells.
{Leukapheresis is a common procedure, which removes only the white blood cells from the
patient.}
Treatment: Once their cells have grown, the patients will be admitted to the hospital for
the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital
for about 4 weeks for the treatment.
Follow up: Patients will return to the clinic for a physical exam, review of side effects,
lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1
year as long as their tumors are shrinking. Follow up visits will take up to 2 days.
...
Clinical Details
Official title: A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Cancers
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determine the rate of tumor regression in patients with metastatic digestive tract and urothelial cancers
Detailed description:
Background:
- Metastatic digestive tract cancers, in particular esophageal, gastric, pancreatic and
hepatobiliary carcinomas, are associated with poor survival beyond five years and poor
response to existing therapies.
- Data from the Surgery Branch and from the literature support that metastatic cancers
are potentially immunogenic and that TIL can be grown and expanded from these tumors.
- In metastatic melanoma, TIL can mediate the regression of bulky disease at any site
when administered to an autologous patient with high dose aldesleukin (IL-2) following
a nonmyeloablative but lymphodepleting chemotherapy preparative regimen.
- The recent young-TIL approach, in which TIL are minimally cultured in vitro, not
selected for tumor recognition, before rapid expansion and infusion to metastatic
melanoma patients, has lead to objective response rates comparable to previous trials
relying on TIL screened for tumor recognition, with no added toxicities.
- We propose to investigate the feasibility, safety, and efficacy of TIL adoptive
transfer therapy for metastatic cancers.
Objectives:
- To determine the ability of autologous TIL infused after minimal in vitro culture in
conjunction with high dose aldesleukin following a non-myeloablative lymphodepleting
preparative regimen to mediate tumor regression in patients with metastatic cancers.
- To determine the phenotypic and functional characteristics of TIL derived from
digestive tract, urothelial, breast, and ovarian/endometrial cancers.
- To determine the toxicity of this treatment regimen.
Eligibility:
Patients who are 18 years of age or older must have:
- Metastatic digestive tract, urothelial, breast, or ovarian/endometrial cancers
refractory to standard chemotherapy, originating from a) gastric or gastroesophageal
junction, or b) pancreas, liver or biliary tree, c) colon or rectum, d) bladder, e)
breast, or f) ovarian/endometrial;
- Normal basic laboratory values.
Patients may not have:
- Concurrent major medical illnesses;
- Severe hepatic function impairment due to liver metastatic burden;
- Unpalliated biliary or bowel occlusion, cholangitis, or digestive tract bleeding;
- Any form of immunodeficiency;
- Severe hypersensitivity to any of the agents used in this study;
- Contraindications for high dose aldesleukin administration.
Design:
- Patients will undergo resection or biopsy to obtain tumor for generation of autologous
TIL cultures and autologous cancer cell lines, and for frozen tissue archive. Lymph
nodes, ascites, peritoneal implants, and normal tissue adjacent to metastatic deposit
will also be obtained when possible for assessing phenotypic and functional
characteristics of TIL derived from digestive tract, urothelial, breast, or
ovarian/endometrial cancers.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide and fludarabineOn day 0 patients will receive the infusion of
autologous TIL and then begin high-dose aldesleukin (720,000 IU/kg IV every 8 hours for
up to 15 doses).
- Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion.
- Twenty-one patients will be initially enrolled in each group to assess toxicity and
tumor responses. If two or more of the first 21 patients per groups shows a clinical
response (PR or CR), accrual will continue to 41 patients, targeting a 20% goal for
objective response.
- Up to 260 patients may be enrolled over 3-8 years
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
1. 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.
2. 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.
3. 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.
4. Clinical performance status of ECOG 0 or 1.
5. Life expectancy of greater than three months.
6. Greater than or equal to 18 years of age and less than or equal to 70 years of age.
7. Willing to practice birth control during treatment and for four months after
receiving the treatment.
8. Willing to sign a durable power of attorney.
9. Able to understand and sign the Informed Consent Document.
10. Hematology:
- Absolute neutrophil count greater than 1000/mm(3) without support of filgrastim.
- Normal WBC (> 3000/mm(3)).
- Hemoglobin greater than 8. 0 g/dl. Subjects may be transfused to reach this
cut-off.
- Platelet count greater than 100,000/mm(3).
- Normal prothrombin time (less than or equal to 15. 2 seconds).
11. Serology:
- Seronegative for HIV antibody. (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive can have decreased immune competence and thus may be less
responsive to the experimental treatment and more susceptible to its
toxicities.)
- 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 RT-PCR and be HCV RNA negative.
12. Chemistry:
- Serum ALT/AST less than five times the upper limit of normal.
- Serum creatinine less than or equal to 1. 6 mg/dl.
- 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.
13. 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.
14. 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.
EXCLUSION CRITERIA:
1. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the treatment on the fetus or infant.
2. Systemic steroid therapy required.
3. 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.
4. Advanced primary with impeding occlusion, perforation or bleeding, dependant on
transfusion.
5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
Disease and AIDS).
6. Concurrent opportunistic infections (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who have decreased immune
competence may be less responsive to the experimental treatment and more susceptible
to its toxicities.)
7. History of severe immediate hypersensitivity reaction to any of the agents used in
this study.
8. History of coronary revascularization or ischemic symptoms.
9. Any patient known to have an LVEF less than or equal to 45%.
10. 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 greater than or equal to 60 years old
11. Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with
known underlying liver dysfunction.
Locations and Contacts
Jessica G Yingling, R.N., Phone: (866) 820-4505, Email: ncisbirc@mail.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center, Phone: 866-820-4505, Email: ncisbirc@mail.nih.gov
Additional Information
NIH Clinical Center Detailed Web Page
Related publications: Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H, Ohuchi A, Ohuchi K, Shiiba K, Kurokawa Y, Satomi S. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer. 2004 Nov 1;91(9):1711-7. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999 Sep;230(3):309-18; discussion 318-21. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D'Angelica M. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007 Oct 10;25(29):4575-80.
Starting date: July 2010
Last updated: April 30, 2015
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