Autologous Dendritic Cells in Treating Patients With Metastatic Kidney Cancer

A Phase I, Open Label, Dose Escalation and Cohort Expansion Study to Evaluate the Safety and Immune Response to Autologous Dendritic Cells Transduced With Ad-GMCAIX in Patients With Metastatic Renal Cell Carcinoma

This phase I trial studies the side effects and best dose of autologous dendritic cells in treating patients with metastatic kidney cancer. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells.

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: AdGMCAIX-transduced autologous dendritic cells; Biological: therapeutic autologous dendritic cells

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of dendritic cell (DC)-AdGM carbonic anhydrase IX (CAIX) administered by intradermal injections at study doses and schedule.

SECONDARY OBJECTIVES:

I. To evaluate clinical antitumor effects following study treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1. Parameters include objective response (complete response [CR], partial response [PR]), duration of response in patients with objective response, and time to disease progression.

II. To evaluate immune responses to DC-AdGMCAIX vaccination by enzyme-linked immunospot (ELISpot) for numeric determination of CAIX specific T cells in blood.

III. To evaluate immune responses to DC-AdGMCAIX vaccination by cytokine profiling of T cell culture supernatants for characterization of the immune response in subjects with demonstrated immune activation may be performed.

IV. To evaluate immune responses to DC-AdGMCAIX vaccination by anti-sargramostim (GM-CSF) antibody response.

V. To evaluate tumor biopsies for immune cell infiltrates.

OUTLINE: This is a dose-escalation study.

Patients receive AdGMCAIX-transduced autologous dendritic cells intradermally (ID) on days 1, 15, and 29.

After completion of study treatment, patients are followed up every 2-3 months for at least 6 months.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed clear cell renal cell carcinoma (ccRCC); pathology report from the original diagnosis of renal cell carcinoma is acceptable; the component of conventional clear cell type > 50% is mandatory
• Evidence of metastatic disease with measurable lesion(s) as defined by RECIST guideline version 1.1 to permit tumor response evaluation; subjects with unresected primary tumors may be enrolled as long as evidence of measurable metastatic disease is also present
• Signed informed consent
• Eastern Cooperative Oncology Group (ECOG) =< 1
• Expected life expectancy >= 6 months
• Serum creatinine < 2 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X upper limit of normal (ULN)
• Total bilirubin < 2 X ULN (except for subjects with documented Gilbert's syndrome who can have total bilirubin < 3.0 mg/dl)
• Hemoglobin >= 10 g/dL
• Absolute neutrophil count >= 1.5 X 10^9 cells/L
• Platelets >= 100 X 10^9/L
• Having recovered from prior surgery, radiation, chemotherapy (cytotoxic and noncytotoxic) to toxicity grade =< 1 or returned to baseline; previous treatment with immunotherapies, cytotoxic drugs, or other targeted agents is permitted; if cytotoxic chemotherapy was previously received, the last dose must be >= 1 month before leukapheresis; for other agents, the last dose must be >= 14 days before leukapheresis
• Negative serum pregnancy test within 7 days prior to enrollment in female subjects with reproductive potential

Exclusion Criteria:

• Rapidly progressing cancer likely to require palliative systemic intervention within 8 weeks after study entry
• Presence of untreated/active central nervous system (CNS) metastases
• For subjects with metastatic RCC who have had no prior systemic treatment for RCC and are considered a poor risk according to Motzer criteria, defined by having >= 3 of the following 5 risk factors for short survival: Karnofsky performance score < 80%, lactate dehydrogenase (LDH) > 1.5 X of ULN, hemoglobin < lower limit of normal (LLN), corrected serum calcium > 10 mg/dL (2.5mM), a time from initial diagnosis of RCC to initiation of systemic therapy of < 1 year
• Non-clear cell or predominantly (> 50%) sarcomatoid histology
• Concurrent major medical conditions, such as uncontrolled hypertension, diabetes mellitus, ischemic heart disease, chronic obstructive pulmonary disease, autoimmune disease, adrenal insufficiency, or prior allogeneic organ transplant requiring chronic immunosuppressive therapy, including systemic glucocorticoid treatment or replacement therapy
• Active or chronic systemic infection, including viral hepatitis, human immunodeficiency virus (HIV), mycobacteria, tuberculosis (TB), or other opportunistic infections
• Having received systemic immune suppressive therapy within 30 days prior to leukapheresis
• Having received an investigational agent within 30 days prior to the first dose of study treatment
• Female subjects who are lactating, pregnant or both male and female subjects with reproductive potential who refuse to practice medically accepted methods for contraception over the period from study consent to 90 days following the last dose of study treatment
• Other malignancy within 3 years, except for adequately treated non-melanoma skin cancer, non-invasive cancers such as cervical or breast carcinoma in situ, or superficial bladder cancer without local recurrence
• Social or psychological conditions that the investigator judges may compromise study compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (autologous dendritic cells); Patients receive AdGMCAIX-transduced autologous dendritic cells ID on days 1, 15, and 29.	Other: laboratory biomarker analysis; Correlative studies; Biological: AdGMCAIX-transduced autologous dendritic cells; Given ID; Other Names: DC-AdGMCAIX; dendritic cells transduced with AdGMCA9 expressing GM-CSF-carbonic anhydrase IX fusion protein; Biological: therapeutic autologous dendritic cells; Given ID; Other Names: ADC; autologous dendritic cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events including all grade 3 and grade 4 adverse events regardless of causality, treatment-related adverse events, dose limiting toxicities (DLT), and adverse events leading to discontinuation of study treatment	Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03	Up to day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAIX-specific immune response	Measured by ELISpot analysis of T cells from blood and cytokine profiling in T cell cultural supernatants.	Up to 3 years
Objective response (CR, PR) according to RECIST guideline version 1.1		Up to 3 years
Duration of progression-free survival		Up to 3 years
Clinical benefit rate (CR, PR, and SD) greater than or equal to 12 weeks		Up to 3 years
Disease response (CR, PR, stable disease [SD], and progressive disease [PD]) according to RECIST guideline version 1		Up to 3 years
Duration of response according to RECIST guideline version 1		Up to 3 years
Time to disease progression		Up to 3 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Kite, A Gilead Company
• Investigators: Principal Investigator: Alexandra Drakaki, MD, Jonsson Comprehensive Cancer Center

Publications and helpful links

General Publications

• Faiena I, Comin-Anduix B, Berent-Maoz B, Bot A, Zomorodian N, Sachdeva A, Said J, Cheung-Lau G, Pang J, Macabali M, Chodon T, Wang X, Cabrera P, Kaplan-Lefko P, Chamie K, Belldegrun AS, Pantuck AJ, Drakaki A. A Phase I, Open-label, Dose-escalation, and Cohort Expansion Study to Evaluate the Safety and Immune Response to Autologous Dendritic Cells Transduced With AdGMCA9 (DC-AdGMCAIX) in Patients With Metastatic Renal Cell Carcinoma. J Immunother. 2020 Nov/Dec;43(9):273-282. doi: 10.1097/CJI.0000000000000336.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2013
• Primary Completion (Actual): July 3, 2018
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: April 4, 2013
• First Submitted That Met QC Criteria: April 4, 2013
• First Posted (Estimate): April 9, 2013

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: 12-000577; NCI-2013-00646 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes