T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Lung Cancer, Skin Cancer, Liver Cancer, Cancer, Brain Cancer, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Oncology |
| Healthy: | No |
| Age Range: | 15 - 70 |
| Updated: | 11/3/2018 |
| Start Date: | October 24, 2013 |
| End Date: | July 28, 2028 |
| Contact: | Margaret Shovlin, R.N. |
| Email: | IRC@nih.gov |
| Phone: | (866) 820-4505 |
Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 Murine TCR-Gene Engineered Lymphocytes
Background:
The NCI Surgery Branch has developed an experimental therapy for treating patients with
cancer that involves taking white blood cells from the patient, growing them in the
laboratory in large numbers, genetically modifying them, and then giving the cells back to
the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type
of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of
the patients who received this treatment experienced shrinking of their tumors. In this
study, we are using a slightly different method of producing the anti-ESO-1 cells which we
hope will be better in making the tumors shrink.
Objectives:
The purpose of this study is to see if these tumor fighting cells (genetically modified
cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to
shrink and to see if this treatment is safe.
Eligibility:
- Patients 15 years old and older with cancer that has the ESO-1 molecule on their tumors.
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
- Leukapheresis: If the patients meet all of the requirements for the study they will
undergo leukapheresis to obtain white blood cells to make the anti ESO-1 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 anti-ESO-1 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 take up to 2
days.
The NCI Surgery Branch has developed an experimental therapy for treating patients with
cancer that involves taking white blood cells from the patient, growing them in the
laboratory in large numbers, genetically modifying them, and then giving the cells back to
the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type
of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of
the patients who received this treatment experienced shrinking of their tumors. In this
study, we are using a slightly different method of producing the anti-ESO-1 cells which we
hope will be better in making the tumors shrink.
Objectives:
The purpose of this study is to see if these tumor fighting cells (genetically modified
cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to
shrink and to see if this treatment is safe.
Eligibility:
- Patients 15 years old and older with cancer that has the ESO-1 molecule on their tumors.
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
- Leukapheresis: If the patients meet all of the requirements for the study they will
undergo leukapheresis to obtain white blood cells to make the anti ESO-1 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 anti-ESO-1 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 take up to 2
days.
PRECIS
Background:
- We have constructed a single retroviral vector that contains both and <= chains of a
murine T cell receptor (mTCR) that recognizes the NY-ESO-1 (ESO) tumor antigen, which
can be used to mediate genetic transfer of this TCR with high efficiency.
- In co-cultures with HLA-A2 and ESO double positive tumors, anti-ESO mTCR transduced T
cells secreted significant amounts of IFN- >= with high specificity.
Primary objective:
- To determine whether the administration of anti-ESO mTCR-engineered peripheral blood
lymphocytes (PBL) plus high-dose aldesleukin following a non-myeloablative lymphoid depleting
preparative regimen may result in objective tumor regression in patients with metastatic
cancers including melanoma expressing the ESO antigen.
Eligibility:
- Age greater than or equal to 15 years and less than or equal to 70 years. Patients aged
15-17 years must weigh at least 50 kg.
- HLA-A*0201 positive
- Metastatic cancer including melanoma whose tumors express the ESO antigen
- Previously received and have been a non-responder to or recurred after receiving
standard care for metastatic disease
- No contraindications for high-dose aldesleukin administration
Patients may not have:
- Contraindications for high dose aldesleukin administration.
Design:
- Peripheral blood mononuclear cells (PBMC) obtained by leukapheresis will be cultured in
the presence of anti-CD3 (OKT3) and aldesleukin to stimulate T-cell growth.
- Transduction is initiated by exposure of cells to retroviral vector supernatant
containing the anti- ESO mTCR genes. This mTCR targets the exact same epitope as the
hTCR.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide and fludarabine.
- On day 0 patients will receive anti-ESO mTCR gene-transduced PBMC and then begin high
dose aldesleukin.
- A complete evaluation of evaluable lesions will be conducted 6 weeks (+/- 2 weeks)
following the administration of the cell product.
- The study will be conducted using a phase II optimal design (Simon R, Controlled
Clinical Trials 10:1-10, 1989). The objective will be to determine if the combination of
high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-ESO TCR-gene
engineered lymphocytes is able to be associated with a clinical response rate that can
rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).
- A total of up to 43 patients may be enrolled (41, plus allowing for up to 2
non-evaluable patients).
Background:
- We have constructed a single retroviral vector that contains both and <= chains of a
murine T cell receptor (mTCR) that recognizes the NY-ESO-1 (ESO) tumor antigen, which
can be used to mediate genetic transfer of this TCR with high efficiency.
- In co-cultures with HLA-A2 and ESO double positive tumors, anti-ESO mTCR transduced T
cells secreted significant amounts of IFN- >= with high specificity.
Primary objective:
- To determine whether the administration of anti-ESO mTCR-engineered peripheral blood
lymphocytes (PBL) plus high-dose aldesleukin following a non-myeloablative lymphoid depleting
preparative regimen may result in objective tumor regression in patients with metastatic
cancers including melanoma expressing the ESO antigen.
Eligibility:
- Age greater than or equal to 15 years and less than or equal to 70 years. Patients aged
15-17 years must weigh at least 50 kg.
- HLA-A*0201 positive
- Metastatic cancer including melanoma whose tumors express the ESO antigen
- Previously received and have been a non-responder to or recurred after receiving
standard care for metastatic disease
- No contraindications for high-dose aldesleukin administration
Patients may not have:
- Contraindications for high dose aldesleukin administration.
Design:
- Peripheral blood mononuclear cells (PBMC) obtained by leukapheresis will be cultured in
the presence of anti-CD3 (OKT3) and aldesleukin to stimulate T-cell growth.
- Transduction is initiated by exposure of cells to retroviral vector supernatant
containing the anti- ESO mTCR genes. This mTCR targets the exact same epitope as the
hTCR.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide and fludarabine.
- On day 0 patients will receive anti-ESO mTCR gene-transduced PBMC and then begin high
dose aldesleukin.
- A complete evaluation of evaluable lesions will be conducted 6 weeks (+/- 2 weeks)
following the administration of the cell product.
- The study will be conducted using a phase II optimal design (Simon R, Controlled
Clinical Trials 10:1-10, 1989). The objective will be to determine if the combination of
high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-ESO TCR-gene
engineered lymphocytes is able to be associated with a clinical response rate that can
rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).
- A total of up to 43 patients may be enrolled (41, plus allowing for up to 2
non-evaluable patients).
- INCLUSION CRITERIA - PATIENTS WITH SOLID TUMOR CANCERS AND MELANOMA:
- Measurable (per RECIST v1.0 criteria) metastatic cancer or locally advanced
refractory/recurrent malignancy including melanoma that expresses ESO as assessed by
one of the following methods: RT-PCR on tumor tissue, immunohistochemistry of resected
tissue, or serum antibody reactive with ESO.
- Confirmation of diagnosis of metastatic cancer including melanoma by the NCI
Laboratory of Pathology.
- Patients must have previously received first-line standard therapy (or effective
salvage chemotherapy regimens) for metastatic disease, if known to be effective for
that disease, and have been either non-responders (progressive disease) or have
recurred.
- 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.Patients with surgically resected brain metastases are eligible.
- 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 (except for toxicities such as alopecia or vitiligo).
Note: Patients may have undergone minor surgical procedures within the past three weeks, as
long as all toxicities have recovered to grade 1 or less.
Note: Patients who have previously received ipilimumab and have documented GI toxicity must
have a normal colonoscopy with normal colonic biopsies.
INCLUSION CRITERIA - PATIENTS WITH MALIGNANT MENINGIOMA:
- Histologically proven recurrent meningioma or aggressive meningioma.
Note: Confirmation of ESO expression and pathology is not required in patients with
definitive radiologic evidence of meningioma who are unresectable, and in whom radiation
therapy without biopsy is the standard treatment.
- Recurrent disease/progression after receiving all standard treatments, which must
include the following:
- Surgical resection, if possible.
- Definitive radiation therapy for unresectable meningioma, or for recurrent
meningioma after resection.
- At least 4 weeks post-surgery, and must be at least 3 months post-radiation therapy,
with resolution of related toxicities.
- Measurable disease on MRI scan.
- No history of intracranial hemorrhage.
- Patients with a history of neurofibromatosis (NF) may have other stable CNS tumors,
such as schwannoma, acoustic neuroma, or ependymoma only if those lesions have been
stable for the past 6 months.
- Patients must be on stable dose of steroids for at least 5 days prior to baseline
imaging.
INCLUSION CRITERIA - ALL PATIENTS:
- Age greater than or equal to 15 years and less than or equal to 70 years..
- Patient, or their parent(s)/legal guardian(s) (if the patient is < 18 years of age),
is able to understand and willing to sign a written informed consent. Written assent
will be obtained for participants under the age of 18 as appropriate.
- All participants greater than or equal to 18 years of age must be willing to sign a
durable power of attorney.
- Clinical performance status of ECOG 0 or 1.
- Patients aged 15-17 years weigh greater than or equal to 50 kg.
- HLA-A*0201 positive.
- Patients of both genders must be willing to practice birth control from the time of
enrollment on this study and for four months after treatment.
- Women of child-bearing potential must have a negative pregnancy test because of the
potentially dangerous effects of the treatment on the fetus.
- Serology
- Seronegative for HIV antibody. (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive may have decreased immune-competence and thus may be less responsive
to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, 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.
- Hematology
- ANC greater than 1000/mm(3) without the support of filgrastim
- WBC greater than or equal to 3000/mm(3)
- Platelet count greater than or equal to 100,000/mm(3)
- Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this
cut-off.
- Chemistry:
- Serum ALT/AST less than or equal to 2.5 times the upper limit of normal
- Serum creatinine less than or equal to 1.6 mg/dl
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert
s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- Subjects must be co-enrolled in protocol 03-C-0277.
EXCLUSION CRITERIA:
- Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the treatment on the fetus or infant.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
Disease).
- Active systemic infections requiring anti-infective treatment, coagulation disorders,
or any other active or uncompensated major medical illnesses.
- Concurrent opportunistic infections (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who have decreased
immunecompetence may be less responsive to the experimental treatment and more
susceptible to its toxicities).
- Concurrent systemic steroid therapy.
- History of severe immediate hypersensitivity reaction to cyclophosphamide,
fludarabine, or aldesleukin.
- History of coronary revascularization or ischemic symptoms.
- Documented LVEF less than or equal to 45% tested in patients:
- Age greater than or equal to 65 years
- With clinically significant atrial and/or ventricular arrhythmias, including but
not limited to: atrial fibrillation, ventricular tachycardia, second- or
third-degree heart block or have a history of ischemic heart disease and/or chest
pain.
- Documented FEV1 less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (greater than or equal to 20 pack-year
smoking history, with cessation within the past two years).
- Symptoms of respiratory dysfunction.
- Patients who are receiving any other investigational agents.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 866-820-4505
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