NeoplasmsPhase 1NCT01081808
Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors
A Phase 1 study testing EGFRBi-armed autologous activated T cells in people with Neoplasms and Tumors, run by Roger Williams Medical Center at 1 site in United States.
Trial summary
RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Tumors, Solid Tumors
- What is being tested?
- EGFRBi-armed autologous activated T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Feb 2015
- 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 solid tumor type (ex. Head and Neck Squamous Cell Carcinoma, Colorectal, Pancreatic, Gastric, Esophageal, Renal, Prostate, Breast and Ovarian cancers, etc.); high risk, recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
- Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC)
- No clinical evidence of active brain metastases; patients with brain metastases are eligible provided they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
- No prior hematological malignancy
- Karnofsky performance status (PS) 60-100% OR RCOG PS 0-2
- Life expectancy ≥ 3 months
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- Not pregnant or nursing
- Fertile patients must use contraception
- Granulocytes ≥ 1,000/mm3
- Platelet count ≥ 50,000/mm3
- Hemoglobin ≥ 8g/dL
- BUN ≤ 2.0 times normal
- Serum creatinine ≤ 2.0mg/dL
- Bilirubin ≤ 1.5 times normal (with or without liver metastases)
- Hepatitis B surface antigen and HIV negative
- LVEF ≥ 45% at rest by MUGA
- No evidence of depressed left ventricular function
- No other malignancy, except for the following:
- History of curatively treated in situ squamous cell carcinoma or basal cell carinoma of the skin
- History of other curatively treated malignancy (except those with a hematologic origin) for with the patient has remained in complete remission > 5 years after completing therapy (as documented by history, physical exams, tumor markers, and radiology scanning)
Who cannot join
- Serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
- Recent myocardial infarction (within the past year)
- Current angina/coronary symptoms requiring medications
- Clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
- Systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 m Hg; patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the infusion
- Clinical evidence of active brain metastases
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- Prior/Concurrent Therapy
- More than 4 weeks since prior chemotherapy or radiotherapy
- At least 4 weeks since prior cetuximab or small molecule EGFR-inhibitors including, but not limited to, gefitinib or erlotinib hydrochloride
- No concurrent radiotherapy
- No concurrent steroids except for treatment or adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions(e.g., insulin for diabetes)
Trial locations and contacts
1 site in 1 country.
United States1 site
Roger Willaims Medical Center
Providence, Rhode Island, 02908
About this study
Official title: A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Solid Tumors
RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic advanced solid tumors.
Read the detailed description
OBJECTIVES:
Primary
Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated T-cells (ATC) when administered in combination with low-dose aldesleukin and sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic) advanced solid tumors.
Secondary
Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
Monitor changes in sera concentrations of the tumor-associated biomarkers respective of the primary neoplasm (i.e. carcinoembryonic antigen(CEA); prostate specific antigen (PSA); Her2/neu (HER2); etc.) in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter.
Monitor patient sera for human anti-mouse antibodies (HAMA).
Evaluate immune response, which may reflect immune augmentation in response to EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well as purified immune cell populations.
Investigate proliferation in response to ex vivo stimulation with tumor-specific antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of EGFR-specific cytotoxic T-lymphocytes (CTL).
OUTLINE: Peripheral blood mononuclear cells (PBMCs) are collected by 1 or 2 leukaphereses for the generation of activated T cells (ATCs). The PBMCs are activated with OKT3 (anti-CD3) and expanded in aldesleukin for up to 14 days. The ATCs are then armed with EGFRBi.
Patients receive EGFRBi-armed autologous ATCs IV over 30-60 minutes twice weekly for 4 weeks (a total of 8 infusions) in the absence of disease progression or unacceptable toxicity. Patients also receive low-dose aldesleukin subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing for 1 week after the last ATC infusion.
After completion of study therapy, patients are followed periodically.
NOTE: For the purpose of determining safety and maximum tolerated dose of EGFRBi-armed ATC, patients enrolled at each dose level from this study will be combined with patients enrolled at each dose level in RWH 349-32 (NCT00569296): A phase I study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer (NSCLC) to count toward each dose level cohort. A total of three patients enrolled form either of the two trials will be treated at each dose level, but at least one NSCLC patient representative from protocol 349-32 will be enrolled and evaluated at each dose level.
- Conditions
- Neoplasms, Tumors, Solid Tumors, Metastatic Cancer
- Being tested
- EGFRBi-armed autologous activated T cells
- Keywords
- PhaseI, Solid Tumor, biomarkers, T cell, Cetuximab, Epidermal Growth Factor Receptor, Aldesleukin, Lymphocytes, Autologous, Recurrent, Refractory, Metastatic, Immunotherapy, Antibodies, Neoplasms by Site, Anti-Retroviral Agents, Therapeutic Uses, Anti-Infective Agents, Neoplasms by Histologic Type, Antineoplastic Agents
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Recurrence, Neoplasms by Site, Neoplasms by Histologic Type, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGFRBi-armed autologous activated T cellsBiological
Also called ATC, IL-2, GM-CSF
EGFRBi-armed autologous activated T cells infused twice a week for 4 weeks for a total of 8 infusions. The doses of the armed ATC will be escalated at the dose levels of 5, 10, 20, and 40 billion armed ATC per infusion. Subcutaneous aldesleukin (300,000IU/m2/day) and Sargramostim (250 ug/m2 twice per week) both starting 3 days before the 1st infusion and ending 7 days after the last dose of armed ATC.
| Study group | Role | What they receive |
|---|---|---|
| Armed Activated T Cells | Other | Activated T Cells (ATC) armed with the bispecific antibody OKT3 x Cetuximab (EGFRBi). ATC will be expanded for 14 days from a leukapheresis product, armed with EGFRBi, cryopreserved and infused in 8 divided doses. Patients will also receive low dose subcutaneous IL-2(3000,000 IU/m2/day) and GM-CSF (250ug/m2 twice per week) Receives: Biological: EGFRBi-armed autologous activated T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
Measured: 5 week regimen with 2 month follow up
Secondary outcomes (6)
Determine potential side effects of treating patients with Armed Activated T Cells (ATC)
Measured: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
Measured: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy
Measured: 5 week regimen with 2 month follow up
Overall survival
Measured: 5 week regimen wtih 2 month follow up
Progression-free survival
Measured: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of peripheral blood lymphocytes
Measured: 5 week regimen with 2 month follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2010 (estimated)
- Study startOct 2009
- Primary completionDec 2014
- Study completionFeb 2015
Why it stopped: Funding ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roger Williams Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abby Maizel, MD,PhD, Study chair, Roger William Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01081808
- Sponsor's protocol ID
- RWH 111-32
- Status last verified
- Mar 2015
- First submitted
- 28 Jan 2010
- Last updated
- 25 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01081808
- Acronym / sponsor ID
- RWH 111-32
- Conditions
- Neoplasms, Tumors, Solid Tumors, Metastatic Cancer
- Keywords
- PhaseI, Solid Tumor, biomarkers, T cell, Cetuximab, Epidermal Growth Factor Receptor, Aldesleukin, Lymphocytes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding ended
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Roger Williams Medical CenterUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 5 Mar 2010 (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.
RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic advanced solid tumors.
Detailed description
OBJECTIVES:
Primary
Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated T-cells (ATC) when administered in combination with low-dose aldesleukin and sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic) advanced solid tumors.
Secondary
Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
Monitor changes in sera concentrations of the tumor-associated biomarkers respective of the primary neoplasm (i.e. carcinoembryonic antigen(CEA); prostate specific antigen (PSA); Her2/neu (HER2); etc.) in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter.
Monitor patient sera for human anti-mouse antibodies (HAMA).
Evaluate immune response, which may reflect immune augmentation in response to EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well as purified immune cell populations.
Investigate proliferation in response to ex vivo stimulation with tumor-specific antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of EGFR-specific cytotoxic T-lymphocytes (CTL).
OUTLINE: Peripheral blood mononuclear cells (PBMCs) are collected by 1 or 2 leukaphereses for the generation of activated T cells (ATCs). The PBMCs are activated with OKT3 (anti-CD3) and expanded in aldesleukin for up to 14 days. The ATCs are then armed with EGFRBi.
Patients receive EGFRBi-armed autologous ATCs IV over 30-60 minutes twice weekly for 4 weeks (a total of 8 infusions) in the absence of disease progression or unacceptable toxicity. Patients also receive low-dose aldesleukin subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing for 1 week after the last ATC infusion.
After completion of study therapy, patients are followed periodically.
NOTE: For the purpose of determining safety and maximum tolerated dose of EGFRBi-armed ATC, patients enrolled at each dose level from this study will be combined with patients enrolled at each dose level in RWH 349-32 (NCT00569296): A phase I study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer (NSCLC) to count toward each dose level cohort. A total of three patients enrolled form either of the two trials will be treated at each dose level, but at least one NSCLC patient representative from protocol 349-32 will be enrolled and evaluated at each dose level.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Armed Activated T Cells | Other | Biological: EGFRBi-armed autologous activated T cellsActivated T Cells (ATC) armed with the bispecific antibody OKT3 x Cetuximab (EGFRBi). ATC will be expanded for 14 days from a leukapheresis product, armed with EGFRBi, cryopreserved and infused in 8 divided doses. Patients will also receive low dose subcutaneous IL-2(3000,000 IU/m2/day) and GM-CSF (250ug/m2 twice per week) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically or cytologically confirmed solid tumor type (ex. Head and Neck Squamous Cell Carcinoma, Colorectal, Pancreatic, Gastric, Esophageal, Renal, Prostate, Breast and Ovarian cancers, etc.); high risk, recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
- Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC)
- No clinical evidence of active brain metastases; patients with brain metastases are eligible provided they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
- No prior hematological malignancy
- Karnofsky performance status (PS) 60-100% OR RCOG PS 0-2
Key exclusion criteria (11 listed)
- Serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
- Recent myocardial infarction (within the past year)
- Current angina/coronary symptoms requiring medications
- Clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
- Systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 m Hg; patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the infusion
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 |
|---|---|---|
| EGFRBi-armed autologous activated T cellsAlso: ATC, IL-2, GM-CSFEGFRBi-armed autologous activated T cells infused twice a week for 4 weeks for a total of 8 infusions. The doses of the armed ATC will be escalated at the dose levels of 5, 10, 20, and 40 billion armed ATC per infusion. Subcutaneous aldesleukin (300,000IU/m2/day) and Sargramostim (250 ug/m2 twice per week) both starting 3 days before the 1st infusion and ending 7 days after the last dose of armed ATC. | Biological | Armed Activated T Cells |
Primary outcome
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
Time frame: 5 week regimen with 2 month follow up
6 secondary outcomes
Determine potential side effects of treating patients with Armed Activated T Cells (ATC)
Time frame: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
Time frame: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy
Time frame: 5 week regimen with 2 month follow up
Overall survival
Time frame: 5 week regimen wtih 2 month follow up
Progression-free survival
Time frame: 5 week regimen with 2 month follow up
Determination of immunologic changes by evaluation of peripheral blood lymphocytes
Time frame: 5 week regimen with 2 month follow up
Results and safety
The study was stopped early (reason given: Funding ended). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2015.
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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.
Abby Maizel, MD,PhD study chair
Roger William Medical 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 EGFRBi-armed autologous activated T cells in people with Neoplasms and Tumors, run by Roger Williams Medical 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 20 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: stopped early, as of the sponsor's last update on 25 Mar 2015. 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 was stopped early (reason given: Funding ended). Results are not available in the source record.
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?
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells (time frame: 5 week regimen with 2 month follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Mar 2015.