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

NCT03354390 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 18001218-H-0012
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Kidney Cancer

Keywords

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

Outcome Measures

Primary Outcomes (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.

  21 days

Secondary Outcomes (4)

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

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

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

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

• Median In Weeks to Progression-free Survival

  Baseline up to Day 192

• Median Overall Survival

  ongoing

Study Arms (4)

Level 1 is 1 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight

EXPERIMENTAL

Participants 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.

Biological: cell infusion

Level 2 is 5 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight

EXPERIMENTAL

Participants 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.

Biological: cell infusion

Level 3 is 1 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight

EXPERIMENTAL

Participants 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.

Biological: cell infusion

Level 4 is 5 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight

EXPERIMENTAL

Participants 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.

Biological: cell infusion

Interventions

cell infusion BIOLOGICAL

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.

Level 1 is 1 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight; Level 2 is 5 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight; Level 3 is 1 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight; Level 4 is 5 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Loyola University Medical Center (LUMC): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 39266213 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Insulin Infusion Systems

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Delivery Systems; Drug Therapy; Therapeutics; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment

Results Point of Contact

• Title: Richard Childs, M.D. Principal Investigator
• Organization: National Heart Lung and Blood Institute (NHLBI)

childsr@nhlbi.nih.gov

301-451-7128

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: November 28, 2017
• Study Start: July 20, 2018
• Primary Completion: October 31, 2023
• Study Completion (Estimated): March 3, 2029
• Last Updated: April 28, 2026
• Results First Posted: December 3, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: At the time of publication or by the end of the protocol, whichever comes first, and available indefinitely.
• Access Criteria: Data will be shared through Figshare, which is an open access repository.

Locations

US (1)