Clear Cell Renal Cell CarcinomaPhase 1NCT01826877
Autologous Dendritic Cells in Treating Patients With Metastatic Kidney Cancer
A Phase 1 study testing AdGMCAIX-transduced autologous dendritic cells, therapeutic autologous dendritic cells and laboratory biomarker analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer
- What is being tested?
- AdGMCAIX-transduced autologous dendritic cells, therapeutic autologous dendritic cells and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2013to 27 May 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
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Being tested
- AdGMCAIX-transduced autologous dendritic cells, therapeutic autologous dendritic cells, laboratory biomarker analysis
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdGMCAIX-transduced autologous dendritic cellsBiological
Also called DC-AdGMCAIX, dendritic cells transduced with AdGMCA9 expressing GM-CSF-carbonic anhydrase IX fusion protein
Given ID
therapeutic autologous dendritic cellsBiological
Also called ADC, autologous dendritic cells
Given ID
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (autologous dendritic cells) | Experimental | Patients receive AdGMCAIX-transduced autologous dendritic cells ID on days 1, 15, and 29. Receives: Biological: AdGMCAIX-transduced autologous dendritic cells; Biological: therapeutic autologous dendritic cells; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to day 57
Secondary outcomes (7)
CAIX-specific immune response
Measured by ELISpot analysis of T cells from blood and cytokine profiling in T cell cultural supernatants.
Measured: Up to 3 years
Objective response (CR, PR) according to RECIST guideline version 1.1
Measured: Up to 3 years
Duration of progression-free survival
Measured: Up to 3 years
Clinical benefit rate (CR, PR, and SD) greater than or equal to 12 weeks
Measured: Up to 3 years
Disease response (CR, PR, stable disease [SD], and progressive disease [PD]) according to RECIST guideline version 1
Measured: Up to 3 years
Duration of response according to RECIST guideline version 1
Measured: Up to 3 years
Time to disease progression
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2013 (estimated)
- Study start14 Jan 2013
- Primary completion3 Jul 2018
- Study completion27 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Kite, A Gilead Company
- Responsible party
- Sponsor
- Investigators
- Alexandra Drakaki, MD, Principal investigator, Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01826877
- Sponsor's protocol ID
- 12-000577
- Other IDs
- NCI-2013-00646
- Status last verified
- Jul 2021
- First submitted
- 4 Apr 2013
- Last updated
- 4 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
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.
PubMed 32925563
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01826877
- Acronym / sponsor ID
- 12-000577
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Kite, A Gilead Company
- Study start
- 14 Jan 2013 (actual)
- Primary completion
- 3 Jul 2018 (actual)
- Study completion
- 27 May 2021 (actual)
- First posted
- 9 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (autologous dendritic cells) | Experimental | Biological: AdGMCAIX-transduced autologous dendritic cells, Biological: therapeutic autologous dendritic cells, Other: laboratory biomarker analysisPatients receive AdGMCAIX-transduced autologous dendritic cells ID on days 1, 15, and 29. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdGMCAIX-transduced autologous dendritic cellsAlso: DC-AdGMCAIX, dendritic cells transduced with AdGMCA9 expressing GM-CSF-carbonic anhydrase IX fusion proteinGiven ID | Biological | Treatment (autologous dendritic cells) |
| therapeutic autologous dendritic cellsAlso: ADC, autologous dendritic cellsGiven ID | Biological | Treatment (autologous dendritic cells) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (autologous dendritic cells) |
Primary outcome
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
7 secondary outcomes
CAIX-specific immune response
Time frame: Up to 3 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
- Derived from this study: PubMed 32925563Faiena 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.
Related trials for Clear Cell Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Active, not recruitingPhase 1/2
Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma.
Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandra Drakaki, MD principal investigator
Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AdGMCAIX-transduced autologous dendritic cells, therapeutic autologous dendritic cells and laboratory biomarker analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by Jonsson Comprehensive Cancer Center at 1 site 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 13 inclusion and 11 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 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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). 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 NCT01826877, 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 4 Aug 2021.