AzTrials
AzTrials

Metastatic Renal Cell CarcinomaPhase 1NCT02035358

Immunotherapy Study for Metastatic Renal Cell Cancer

A Phase 1 study testing HyperAcute®-Renal (HAR) Immunotherapy in people with Metastatic Renal Cell Carcinoma and Metastatic Clear-cell Renal Cancer, run by NewLink Genetics Corporation at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

In this Phase 1 Trial investigators plan to establish the MTD of HyperAcute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
HyperAcute®-Renal (HAR) Immunotherapy
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesUnited States
Study dates
May 2015to 12 Jan 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years or older
  • Signed written informed consent
  • Diagnosis of RCC with clear-cell or predominant clear-cell histology (≤ 50% other histologic features)
  • Subjects with recurrent or refractory, metastatic disease (N1 or M1) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading
  • pT3, G any, N1; or, pT4, G any, N1; or, pT any, G any, N1 or M1)
  • Subjects have already undergone all standard of care surgery appropriate for stage of disease.
Show all 15Show fewer
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
  • Serum albumin ≥3.0 gm/dL.
  • Adequate organ function including:
  • Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3, platelets ≥75,000/mm3, absolute lymphocyte count ≥475/mm3.
  • Hepatic: Serum total bilirubin ≤2.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤2.5 x ULN.
  • Renal: Serum creatinine (sCr) ≤ 2.0 x upper limit of normal.
  • Patients must have the ability to understand the study, its risks, side effects, potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA).
  • Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last immunization.
  • Patients who have received previous systemic therapies including TKI inhibitors are eligible.

Who cannot join

  • Age <18-years-old.
  • Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ≥1 month are eligible.
  • Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
  • Other malignancy within five years, except that the following may be eligible:
  • patients curatively treated for localized squamous or basal cell carcinoma of the skin or for carcinoma in situ of the uterine cervix (CIN) or breast,
  • Patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated.
Show all 26Show fewer
  • History of an allogeneic solid organ transplant or bone marrow transplant, or current active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
  • Subjects taking systemic (parentally or orally) corticosteroid therapy for any reason, including replacement therapy for hypoadrenalism, are not eligible. Topical steroids are acceptable as are intranasal steroids.
  • Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.
  • Evidence of active autoimmune disease (e.g., systemic lupus erythematosis, rheumatoid arthritis, with the exception of vitiligo. Patients with a remote history of asthma or mild asthma are eligible.
  • Other serious medical conditions that may be expected to limit life expectancy to less than 1 year (e.g., liver cirrhosis).
  • Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc).
  • Patients having previously undergone splenectomy.
  • Patients with known hepatitis or unstable liver disease, and/or positive serologies for Hepatitis B or C and HIV.
  • Patients with sickle-cell anemia or thalassemia major.
  • History of any one or more of the following cardiovascular conditions within the past 6 months:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  • Concurrent investigational therapy given to treat cancer or concurrent participation in another clinical trial involving anti-cancer investigational drug.
  • Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • John Hopkins University

    Baltimore, Maryland, 21205

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Univeristy of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: A Phase I Study of HyperAcute-Renal (HAR) Immunotherapy In Patients With Metastatic Renal Cell Cancer

In this Phase 1 Trial investigators plan to establish the MTD of HyperAcute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma.

Read the detailed description

Unfortunately, despite the best clinical efforts with surgical intervention and chemotherapy many patients with high grade and advanced stage renal cell carcinoma (RCC) progress and die of their disease. In United States approximately 13,000 individuals die from RCC each year. The primary cause of failure is microscopic spread of the tumor prior to complete surgical extirpation of detectable disease and the heterogenous nature of the metastatic cells. These cells are resistant to all forms of therapy including chemotherapy, radiation, and escape from immune surveillance by a variety of mechanism. This results in low 5-year survival rates (approximately 10%) in patients with metastasis. Novel immunotherapeutic strategies provide a hope in circumventing the drug resistant RCC and improve the survival of patients undergoing surgery. RCC, like melanoma is one of the most immunogenic tumors and partial successes have been achieved by a variety of immunotherapeutic strategies show partial successes. Although vaccines have been highlighted in clinical trials since the mid-1970s with subcutaneous autologous irradiated tumor cells most of these studies were in patients with advanced disease. These approaches resulted in rare if any clinically relevant benefits to patients. However, new vaccines in other cancers have shown responses equivalent to chemotherapy with minimal toxicity [1]. The use of immune adjuvant strategies to increase the therapeutic immune responses to tumor vaccines enhanced the proportion of patients with therapeutic responses to vaccination to 10%-15% on average. Only during the last decade has it become clear that failure of immune system to respond to the tumor vaccine is the main obstacle that limits the efficacy of vaccine based immunotherapies. The precise reason for failure of the immune system in cancers is very complex particularly as it relates to (1) the escape of growing or metastasizing tumor from immune surveillance [2-4] and (2) low immunogenicity of autoantigens associated with malignant neoplasms. This human clinical trial will investigate the dose limiting toxicity of a polyvalent immune enhanced vaccine as a first step towards developing a multipronged approach to triggering the immune system to attack and destroy micrometastatic disease. Investigators hypothesize that the allogeneic RCC cell genetically modified to express α (1,3)galactosyltransferase (enzyme responsible for producing the strong xenoantigen on the cell surface of the cellular immunotherapy) will augment the efficacy of cellular immunotherapy and thereby improve patient outcomes. In this Phase 1 Trial investigators plan to establish the maximum tolerated dose (MTD) of Hyperacute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma.

Being tested
HyperAcute®-Renal (HAR) Immunotherapy
Keywords
Metastatic, Recurrent, Refractory, Renal Cell Carcinoma, Kidney, clear-cell renal cancer, Cancer
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms, Neoplasm Metastasis, Recurrence, Neoplasms

What participants receive

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

  • HyperAcute®-Renal (HAR) ImmunotherapyBiological

    Also called HyperAcute®-Renal, HAR

    HyperAcute®-Renal Immunotherapy consisting of equal cell doses of each of two allogeneic renal cell cancer cell lines (HAR1 and HAR2) engineered to express the murine α(1,3)GT gene.

    Cells will be injected intradermally every 1 week x 4 weeks and then every 2 weeks for 10 immunizations to total 14 immunizations. Dose Cohort 1 will receive 150 million cells per immunization; Dose Cohort 2 will receive 300 million cells per immunization.

Study groups in NCT02035358
Study groupRoleWhat they receive
HyperAcute®-Renal ImmunotherapyExperimentalCells will be injected intradermally every 1 week x 4 weeks and then every 2 weeks for 10 immunizations to total 14 immunizations. Dose Cohort 1 will receive 150 million cells per immunization; Dose Cohort 2 will receive 300 million cells per immunization. Once the first three months of immunizations are completed, patients may receive other systemic treatment (non-investigational) while continuing to receive the remaining 6 immunizations.
Receives: Biological: HyperAcute®-Renal (HAR) Immunotherapy

What is being measured

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

  1. Percentage of patients with adverse events

    To determine the toxicity (side-effects, dose-limiting toxicity [DLT] and maximum tolerated dose [MDT]) of administration of HyperAcute®- Renal (HAR) immunotherapy cells administered by intradermal injection into patients with recurrent or refractory, metastatic clear-cell renal cancer.

    Measured: 3 months

Secondary outcomes (2)

  1. Immunological Correlative Studies

    To conduct correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect. In these studies human humoral and cellular immune responses to HAR cells will be evaluated in blood specimens pre and post immunotherapy for microenvironmental immune modulation.

    Measured: 3 months

  2. Progression-Free Survival

    To assess the tumor response rate (progression-free survival) of anti-tumor immunization with HyperAcute®-Renal.

    Measured: 3 months

Timeline

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

  1. First posted14 Jan 2014 (estimated)
  2. Study startMay 2015
  3. Primary completion3 Jan 2017
  4. Study completion12 Jan 2021

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02035358
Sponsor's protocol ID
NLG0106
Status last verified
Apr 2022
First submitted
10 Jan 2014
Last updated
6 Apr 2022
Results posted
No

Publications

  • Hahn AW, Drake C, Denmeade SR, Zakharia Y, Maughan BL, Kennedy E, Link C Jr, Vahanian N, Hammers H, Agarwal N. A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma. Oncologist. 2020 Feb;25(2):121-e213. doi: 10.1634/theoncologist.2019-0599. Epub 2019 Sep 6.

    PubMed 32043778

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HyperAcute®-Renal (HAR) Immunotherapy in people with Metastatic Renal Cell Carcinoma and Metastatic Clear-cell Renal Cancer, run by NewLink Genetics Corporation at 3 sites 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 15 inclusion and 26 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: finished, as of the sponsor's last update on 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Percentage of patients with adverse events (time frame: 3 months). 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 NCT02035358, 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 6 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in