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Autologous Dendritic Cells in Treating Patients With Metastatic Kidney Cancer

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ClinicalTrials.gov Identifier: NCT01826877
Recruitment Status : Completed
First Posted : April 9, 2013
Last Update Posted : August 4, 2021
Sponsor:
Collaborator:
Kite, A Gilead Company
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE April 4, 2013
First Posted Date  ICMJE April 9, 2013
Last Update Posted Date August 4, 2021
Actual Study Start Date  ICMJE January 14, 2013
Actual Primary Completion Date July 3, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2013)
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 [ Time Frame: Up to day 57 ]
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2013)
  • CAIX-specific immune response [ Time Frame: Up to 3 years ]
    Measured by ELISpot analysis of T cells from blood and cytokine profiling in T cell cultural supernatants.
  • Objective response (CR, PR) according to RECIST guideline version 1.1 [ Time Frame: Up to 3 years ]
  • Duration of progression-free survival [ Time Frame: Up to 3 years ]
  • Clinical benefit rate (CR, PR, and SD) greater than or equal to 12 weeks [ Time Frame: Up to 3 years ]
  • Disease response (CR, PR, stable disease [SD], and progressive disease [PD]) according to RECIST guideline version 1 [ Time Frame: Up to 3 years ]
  • Duration of response according to RECIST guideline version 1 [ Time Frame: Up to 3 years ]
  • Time to disease progression [ Time Frame: Up to 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Dendritic Cells in Treating Patients With Metastatic Kidney Cancer
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Clear Cell Renal Cell Carcinoma
  • Recurrent Renal Cell Cancer
  • Stage IV Renal Cell Cancer
Intervention  ICMJE
  • 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
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (autologous dendritic cells)
Patients receive AdGMCAIX-transduced autologous dendritic cells ID on days 1, 15, and 29.
Interventions:
  • Biological: AdGMCAIX-transduced autologous dendritic cells
  • Biological: therapeutic autologous dendritic cells
  • Other: laboratory biomarker analysis
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 2, 2018)
12
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2013)
18
Actual Study Completion Date  ICMJE May 27, 2021
Actual Primary Completion Date July 3, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01826877
Other Study ID Numbers  ICMJE 12-000577
NCI-2013-00646 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE Kite, A Gilead Company
Investigators  ICMJE
Principal Investigator: Alexandra Drakaki, MD Jonsson Comprehensive Cancer Center
PRS Account Jonsson Comprehensive Cancer Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP