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Protocol Details

A Phase I Study of HERV-E TCR Transduced Autologous T Cells in Patients with Metastatic Clear Cell Renal Cell Carcinoma

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-H-0012

Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 70

Referral Letter Required

Yes

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

genetically modified lymphocytes;
tumor antigens;
T cell receptor immunotherapy;
genomic retroviral elements

Recruitment Keyword(s)

None

Condition(s)

Kidney Cancer

Investigational Drug(s)

HERV-E TCR

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: cell infusion

Supporting Site

National Heart, Lung, and Blood InstituteLoyola University Medical Center (LUMC)

Background:

Gene transfer is a new cancer therapy takes white blood cells from a person and grows them in a lab. The cells are changed with a virus to attack tumor cells, then returned to the person. Researchers want to see if this therapy fights kidney cancer cells.

Objective:

To see if gene transfer is safe and causes tumors to shrink.

Eligibility:

People at least 18 years old with certain kidney cancer

Design:

Participants will be screened with blood and urine tests. They may have:

-Scans

-Heart, lung, and eye tests

-Lab tests

-Tumor samples taken

Participants will have leukapheresis. Blood will be removed by a needle in an arm. It will go through a machine that removes white blood cells. Plasma and red cells will be returned through a needle in the participant s other arm.

Participants cells will be grown in the lab and genetically changed.

Participants will stay in the hospital 2 3 weeks. There they will:

-Get 2 chemotherapy drugs by catheter (thin plastic tube) inserted into a vein in the chest.

-Get the changed cells via catheter.

-Get a drug to increase white blood cell count and one to make the cells active.

-Recover for about a week.

-Have lab and blood tests.

After leaving the hospital, participants will:

-Take an antibiotic for several months.

-Have leukapheresis.

-Have one- or two-day clinic visits every few weeks for 2 years, and then as determined by their doctor. These will include blood and lab tests, imaging studies, and physical exam.

Participants will have follow-up checks for up to 15 years.

Sponsoring Institute: National Heart, Lung, and Blood Institute

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Eligibility

INCLUSION CRITERIA:

-Patients must have histologically confirmed RCC with clear-cell component by the Laboratory of Pathology of 43T the NIH prior to entering this study.

-Patients must be HLA-A 11:01 positive (confirmed by HLA typing at the NIH DTM)

-Patients must have measurable disease and have disease progression during or after the last treatment regimen and within 6 months before study enrollment

-Patients must have received at least one antiangiogenic drug and an immune-checkpoint inhibitor (i.e. nivolumab) unless the patient has contraindications to receiving these medications, the agents are not available to the patient, or the patient declines to receive these drugs due to personal preference.

-Patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 180 days (female patients) or 90 days (male patients) after the end of the treatment if sexually active and able to bear or beget children. In addition, male patients must refrain from sperm donation for 90 days after the final dose of investigational product. Female patients must refrain from egg cell donation for 180 days after the final dose of investigational product

-Patients must be between the ages of 18 and 70 years.

-Patient must have an anticipated life expectancy of at least 3 months.

-Patients must have a performance status of 0 or 1 ECOG performance status (PS) scale.

-Patients must have a caregiver willing to stay with them during the first month of treatment (30 days +/- 7 days).

-Patients receiving treatment with bisphosphonates or denosumab are eligible for enrollment if on a stable dose for greater than or equal to 4 weeks

-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 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.

-Organ Function

--Hematology

--Absolute neutrophil count greater than or equal to 1000/ microL

--WBC greater than or equal to 3000/microL

--Platelet count greater than or equal to 100.000/microL (without transfusional support)

--Hemoglobin greater than or equal to 8gr/dl (without transfusional support)

--Chemistry

--Serum AST/ALT less than or equal to 2.5 x upper limit of normal (ULN)

--Total bilirubin less than or equal to 1.5 mg/dl except for patients with Gilbert s syndrome who must have a total bilirubin less than or equal to 3 mg/dl

--Calculated creatinine clearance by the method of CKI-EPI greater than or equal to 50 ml/min/1.73m2

--INR < 1.5

--Cardiology

--Estimated left ventricular ejection fraction by echocardiography greater than or equal to 45%

--Respiratory

--Predicted DLCO / Alveolar Volume Adjusted by PFT > 45%

-Patients must have the ability to provide written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time.

EXCLUSION CRITERIA:

-Patients that require immediate therapy due to tumor mass effects or spinal cord compression.

-Patients must not have had standard of care anti-VEGFR therapy (mean half-life around 30 hours), mTOR inhibitors (mean half-life around 30 hours), radiotherapy, or major surgery within the last 2 weeks prior to T-cell infusion. For PD-1/PD-L1 inhibitors or CTLA-4 inhibitors, a 4-week period must have elapsed before T-cell infusion. For recent experimental therapies a 28-day period must have elapsed before infusing expanded T-cells.

-Patients with active CNS involvement by malignancy either by imaging or cerebrospinal fluid involvement or biopsy-proven (due to poor prognosis and potential for neurological dysfunction that would confound evaluation of neurological and other adverse events) except for:

a) Patients with single brain metastases of <1cm treated with either stereotactic or gamma knife radiotherapy and remained stable on MRI for 2 weeks are eligible.

b) Patients with 3 or fewer brain metastases of <1cm treated with either stereotactic or gamma knife radiotherapy and remained stable on MRI for 4 weeks are eligible.

c) Patients with surgically resected brain metastases and no evidence of active disease in the CNS at the time of screening evaluation are eligible.

d) These patients may be enrolled at the discretion of the Principal Investigator

-Patients with hypercalcemia (>10 mg/dL) of malignancy.

-Patients with hypercalcemia (>2.5 mmol/L) of malignancy.

-Any prior Grade greater than or equal to 3 immune-related adverse event (irAE) while receiving immunotherapy, including anti-

CTLA4 treatment, or any unresolved irAE > Grade 1. Note: Active or history of vitiligo or hypothyroidism will not be a basis for exclusion.

-Patients with second malignancies in addition to their clear cell RCC are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 4 years or is not in complete remission. There are exceptions to this criterion: successfully treated non-metastatic basal cell, squamous cell skin carcinoma, in situ non-invasive cervical cancer and in situ non-invasive breast cancer.

-Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

-Active uncontrolled systemic infections (defined as infections causing fevers and/or infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours).

-Active coagulation disorders or other major uncontrolled medical illnesses of the respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, active obstructive or restrictive pulmonary disease, active autoimmune diseases such as rheumatoid arthritis.

-Patients who have recent history of cerebrovascular accident, transient ischemic attack should be cleared by the neurology consult service before enrolling this study.

-Patients who have recent history of coronary artery disease or cardiac arrhythmia should be cleared by the cardiology consult service before enrolling this study.

-Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

-Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus erythematosus that requires treatment with chronic immunosuppressive therapy.

-Systemic corticosteroid steroid therapy of any dose is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. The following are exceptions to this criterion:

--Intranasal, inhaled, and topical steroids

--Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent

-Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

In the case of short-term use of systemic corticosteroids (less than 24 hours within 28 days) of greater than 10 mg/day of prednisone or an equivalent corticosteroid, the required washout period prior to starting the leukapheresis is 7 days.

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

-Unable to understand the investigational nature of the study or give informed consent and does not have a legally authorized representative or surrogate that can provide informed consent.

-Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Richard W. Childs, M.D.
National Heart, Lung and Blood Institute (NHLBI)



Kristen E. Wood, R.N.
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room 44350
10 Center Drive
Bethesda, Maryland 20892
(301) 827-2977
kristen.gunn@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03354390

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