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Kidney CancerPhase 1NCT03354390

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma

A Phase 1 study testing cell infusion in people with Kidney Cancer, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Kidney Cancer
What is being tested?
cell infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
20 Jul 2018to 3 Mar 2029
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed RCC with clear-cell component by the Laboratory of Pathology of the NIH and/or outside Pathology Department 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 per RECIST version 1.1 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 75 years.
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  • 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 500/ microL
  • WBC greater than or equal to 1500/microL
  • Platelet count greater than or equal to 75.000/microL (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
  • Creatinine clearance greater than or equal to 50 ml/min/1.73m^2 by the method of CKI-EPI or >=50 ml/min by the method of 24h Clearence of Creatinine Calculation
  • 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%

Who cannot join

  • 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), at least for the last 7 days prior to T-cell infusion and 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:
  • Patients with 3 or fewer brain metasteses of <1cm treated with either stereotactic or gamma knife radiotherapy and remained stable on MRI for 2 weeks are eligible.
  • Patients with surgically resected brain metastases and no evidence of active disease in the CNS at the time of screening evaluation are eligible.
  • Patients with hypercalcemia (>10 mg/dL) of malignancy.
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  • Any prior Grade greater than or equal to 3 immune-related adverse event (irAE) while receiving immunotherapy, including anti-CTLA4 treatment that requires long-term immunosuppressive therapy. 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 systemic treatment 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 coagulation disorders or other major uncontrolled medical illnesses of the respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, uncontrolled systemic infection, active obstructive or restrictive pulmonary disease.
  • 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 2 days prior to enrollment.
  • 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).
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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.

Read more

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.

Read the detailed description

Metastatic renal cell carcinoma (RCC) is an incurable condition. Current therapy for this disease consists of the serial administration of agents such as VEGF, mTOR inhibitors and immunotherapy (high-dose (HD) IL-2 or immune-checkpoint inhibitors). Long-term survival can be achieved with high-doses IL-2 or immune-checkpoint inhibitors. However, of those patients treated with immunotherapy, three quarters will not respond at all and only 5-8% will achieve a complete and durable response.

Allogeneic hematopoietic stem cell transplantation is also capable of inducing prolonged disease regression in patients with metastatic clear cell RCC (ccRCC). In vitro studies have established that transplanted donor T-cells targeting antigens expressed on RCC cells mediate these anti-tumor effects. However, hematopoietic stem cell transplantation can be toxic and associated with a 10-20% risk of procedure-related mortality. The observation that transplanted donor T-cells have the potential to cure a subset of patients with metastatic disease forms the basis for continued efforts in our laboratory to harness the power of T-cells to cure this disorder.

Our team isolated a tumor-specific cytotoxic T lymphocyte (CTL) line from peripheral blood mononuclear cells (PBMCs) obtained after an allogeneic transplant from a patient who showed prolonged tumor regression. Using limiting dilution cloning, we identified an allogeneic (derived from the stem cell donor) CD8+ T-cell clone that killed ccRCC cells in an HLA A11 restricted fashion. Using cDNA expression cloning, we identified a HERV-E derived antigen expressed in the patient s ccRCC cells to be the target of this T-cell clone. Remarkably, we found this HERV-E was expressed in the majority of ccRCC cells with no expression in normal tissues. Based on the identification of the antigenicity of the HERV-E transcripts in ccRCC, our team in collaboration with Dr. Nishimura s laboratory (Loyola University Cardinal Bernardin Cancer Center) has cloned, expressed and characterized the TCR from this CD8+ T-cell clone that recognizes an HLA A11 restricted HERV-E antigen.

This research protocol is therefore designed to evaluate the safety and effectiveness of infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells in HLA-A*11:01 positive patients with metastatic clear cell RCC. Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide and fludarabine followed by an infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells. To mediate T cell survival and sustain function, moderate-doses of IL-2 (aldesleukin) will be administered intravenously twice a day for 14 doses.

The primary endpoint is safety by day 21. Secondary endpoints will include overall response rate, progression-free survival and overall survival. Exploratory studies will include persistence of circulating HERV-E TCR transduced CD8+/CD34+ enriched T cells, changes in immune cell subsets and activation status of T cells, as well as, other immunologic determinants with clinical outcomes at baseline, at different time points during treatment and at the time of disease progression.

Conditions
Kidney Cancer
Being tested
cell infusion
Keywords
genetically modified lymphocytes, tumor antigens, T cell receptor immunotherapy, genomic retroviral elements
Medical subject headings
Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cell infusionBiological

    This is a phase 1 trial of HERV-E TCR transduced CD8+/CD34+ T cells in HLA-A*11:01 positive patients with metastatic ccRCC. The study is planned based on a Phase 1 3+3 dose escalation design. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 or 1 patient in six has experienced a dose limiting toxicity (DLT). Patients with evaluable advanced/metastatic ccRCC will be recruited in up to 4 dose levels.

Study groups in NCT03354390
Study groupRoleWhat they receive
Level 1 is 1 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimentalParticipants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Receives: Biological: cell infusion
Level 2 is 5 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimentalParticipants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Receives: Biological: cell infusion
Level 3 is 1 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimentalParticipants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Receives: Biological: cell infusion
Level 4 is 5 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimentalParticipants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Receives: Biological: cell infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities

    Toxicity profile at least possible attributed to treatment regime for each dose level using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 except for hematological toxicities

    Toxicity profile as measured by using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) for grade 2 and above. According to https://ctep.cancer.gov/, CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE grades are defined as:

    Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living.

    Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

    Grade 4 Life-threatening consequences; urgent intervention indicated.

    Measured: 21 days

Secondary outcomes (4)

  1. Overall Response Rate Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1)

    The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria.

    Partial Response (PR): > 30% decrease in SUL peak; minimum 0.8 unit decrease. Verification with follow-up study if anatomic criteria indicate disease progression.

    Progressive Disease (PD): > 30% increase in SUL peak (minimum 0.8 unit increase in SUL peak), > 75% increase in TLG of the 5 most active lesions, Visible increase in extent of FDG uptake, or new lesions. Verification with follow-up study if anatomic criteria indicate complete or partial response.

    Stable Disease (SD): Does not meet other criteria.

    Measured: Baseline until date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to Day 127

  2. Overall Duration of Response (Days) Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1)

    Overall duration of response (days) based on the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

    The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Baseline until date of first documented response assessed up to Day 127

  3. Median In Weeks to Progression-free Survival

    Median in weeks of Progression-free survival. Progression-free survival is defined as from the time of initiation of treatment to the occurrence of disease progression or death, whichever occurs first.

    Disease progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (RECIST 1.1), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: Baseline up to Day 192

  4. Median Overall Survival

    Median Overall Survival. Overall survival is defined as the time from treatment initiation to death from any cause.

    Measured: ongoing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2017
  2. Study start20 Jul 2018
  3. Primary completion31 Oct 2023
  4. Study completion3 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03354390
Sponsor's protocol ID
180012
Other IDs
18-H-0012
Status last verified
Apr 2026
First submitted
23 Nov 2017
Last updated
28 Apr 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication

Publications

  • Barisic S, Brahmbhatt EM, Cherkasova E, Spear TT, Savani U, Pierre S, Scurti GM, Chen L, Igboko M, Nadal R, Zeng G, Parry G, Stroncek DF, Highfill S, Dalheim AV, Reger R, Nishimura MI, Childs RW. Regression of renal cell carcinoma by T cell receptor-engineered T cells targeting a human endogenous retrovirus. J Immunother Cancer. 2024 Sep 11;12(9):e009147. doi: 10.1136/jitc-2024-009147.

    PubMed 39266213

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cell infusion in people with Kidney Cancer, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities (time frame: 21 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03354390, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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