Immunotherapy Study for Metastatic Renal Cell Cancer

NCT02035358 | Completed Phase 1

• 1 other identifier: NLG0106
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Metastatic Renal Cell Carcinoma; Metastatic Clear-cell Renal Cancer; Recurrent Renal Cell Carcinoma; Refractory Renal Cell Carcinoma; Metastatic Kidney Cancer

Keywords

Metastatic; Recurrent; Refractory; Renal Cell Carcinoma; Kidney; clear-cell renal cancer; Cancer

Outcome Measures

Primary Outcomes (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.

  3 months

Secondary Outcomes (2)

• Immunological Correlative Studies

  3 months

• Progression-Free Survival

  3 months

Study Arms (1)

HyperAcute®-Renal Immunotherapy

EXPERIMENTAL

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. 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.

Biological: HyperAcute®-Renal (HAR) Immunotherapy

Interventions

HyperAcute®-Renal (HAR) Immunotherapy BIOLOGICAL

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.

Also known as: HyperAcute®-Renal, HAR

HyperAcute®-Renal Immunotherapy

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (3)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

John Hopkins University

Baltimore, Maryland, 21205, United States

Location

Univeristy of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 32043778 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasm Metastasis; Recurrence; Neoplasms

Interventions

cell-surface retention-binding protein 1; Immunotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Design

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

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 14, 2014
• Study Start: May 1, 2015
• Primary Completion: January 3, 2017
• Study Completion: January 12, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-04

Locations

US (3)