Liver CancerPhase 1/2NCT02541370
Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133
A Phase 1/2 study testing anti-CD133-CAR vector-transduced T cells in people with Liver Cancer and Pancreatic Cancer, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cancer, Pancreatic Cancer, Brain Tumor
- What is being tested?
- anti-CD133-CAR vector-transduced T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Jun 2015to Jun 2019
- Phase
- Phase 1/2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chemotherapy refractory or relapsed CD133-positive liver cancer, pancreatic cancer, brain tumor ,breast cancer, ovarian tumors, colorectal cancer and acute leukemia.
- Patients must be 18 years of age or older.
- Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
- Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:
- Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).
- Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m.
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- Seronegative for HIV antibody.
- Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
- Patients must be willing to practice birth control during and for four months following treatment. NOTE: women of child-bearing age must have evidence of negative pregnancy test.
- Patients must be willing to sign an informed consent.
Who cannot join
- 1. Patients with life expectancy less than 12 months will be excluded. 2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.
- 3. Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
- 4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
- 5. Pregnant and/or lactating women will be excluded. 6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
- 7. Patients with any type of primary immunodeficiencies will be excluded from the study.
- 8. Patients requiring corticosteroids (other than inhaled) will be excluded. 9. Patients with history of T cell tumors will be excluded. 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
- 11. Patients with relapsed acute leukemia after allogeneic stem cell transplantation
Trial locations and contacts
1 site in 1 country.
China1 site
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
About this study
Official title: Clinical Study of Chimeric CD(Cluster of Differentiation)133 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Malignancies
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with Relapsed and/or Chemotherapy Refractory Advanced Malignancies.
Read the detailed description
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD133 (cluster of differentiation antigen 133 ) vector (referred to as CART-133 cells).
II. Determine duration of in vivo survival of CART-133 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-133 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to CART-133 cell infusions.
II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-133 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-133 cells to tumor in bone marrow and lymph nodes.
IV. For patients with stored or accessible tumor cells determine tumor cell killing by CART-133 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD133, and assess correlation with loss of detectable CART-133 (loss of engraftment).
VI. Determine the relative subsets of CART-133 T cells (Tcm, Tem, and Treg).
- Conditions
- Liver Cancer, Pancreatic Cancer, Brain Tumor, Breast Cancer, Ovarian Tumor, Colorectal Cancer
- Being tested
- anti-CD133-CAR vector-transduced T cells
- Medical subject headings
- Liver Neoplasms, Pancreatic Neoplasms, Brain Neoplasms, Breast Neoplasms, Ovarian Neoplasms, Colorectal Neoplasms, Leukemia, Lymphoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD133-CAR vector-transduced T cellsBiological
Also called genetically engineered lymphocyte therapy
genetically engineered lymphocyte therapy
| Study group | Role | What they receive |
|---|---|---|
| anti-CD133 CAR T cells | Experimental | Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.
Patients receive anti-CD133-CAR retroviral vector-transduced autologous-derived T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity. Receives: Biological: anti-CD133-CAR vector-transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical
Measured: Until week 24
Secondary outcomes (1)
Anti-tumor responses to CART-133 cell infusions
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2019
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02541370
- Sponsor's protocol ID
- s2015-080-03
- Status last verified
- Jun 2015
- First submitted
- 2 Sep 2015
- Last updated
- 17 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dai H, Tong C, Shi D, Chen M, Guo Y, Chen D, Han X, Wang H, Wang Y, Shen P. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020 Nov 25;9(1):1846926. doi: 10.1080/2162402X.2020.1846926.
PubMed 33312759Feng KC, Guo YL, Liu Y, Dai HR, Wang Y, Lv HY, Huang JH, Yang QM, Han WD. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017 Jan 5;10(1):4. doi: 10.1186/s13045-016-0378-7.
PubMed 28057014
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Chimeric CD(Cluster of Differentiation)133 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Malignancies
- ClinicalTrials.gov ID
- NCT02541370
- Acronym / sponsor ID
- s2015-080-03
- Conditions
- Liver Cancer, Pancreatic Cancer, Brain Tumor, Breast Cancer, Ovarian Tumor, Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 4 Sep 2015 (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: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with Relapsed and/or Chemotherapy Refractory Advanced Malignancies.
Detailed description
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD133 (cluster of differentiation antigen 133 ) vector (referred to as CART-133 cells).
II. Determine duration of in vivo survival of CART-133 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-133 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to CART-133 cell infusions.
II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-133 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-133 cells to tumor in bone marrow and lymph nodes.
IV. For patients with stored or accessible tumor cells determine tumor cell killing by CART-133 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD133, and assess correlation with loss of detectable CART-133 (loss of engraftment).
VI. Determine the relative subsets of CART-133 T cells (Tcm, Tem, and Treg).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-CD133 CAR T cells | Experimental | Biological: anti-CD133-CAR vector-transduced T cellsDose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Patients receive anti-CD133-CAR retroviral vector-transduced autologous-derived T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Chemotherapy refractory or relapsed CD133-positive liver cancer, pancreatic cancer, brain tumor ,breast cancer, ovarian tumors, colorectal cancer and acute leukemia.
- Patients must be 18 years of age or older.
- Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
- Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:
- Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).
Key exclusion criteria (7 listed)
- 1. Patients with life expectancy less than 12 months will be excluded. 2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.
- 3. Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
- 4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
- 5. Pregnant and/or lactating women will be excluded. 6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
- 7. Patients with any type of primary immunodeficiencies will be excluded from the study.
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 |
|---|---|---|
| anti-CD133-CAR vector-transduced T cellsAlso: genetically engineered lymphocyte therapygenetically engineered lymphocyte therapy | Biological | anti-CD133 CAR T cells |
Primary outcome
Occurrence of study related adverse events
Time frame: Until week 24
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical
1 secondary outcome
Anti-tumor responses to CART-133 cell infusions
Time frame: up to 24 weeks
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 17 Dec 2019.
- Derived from this study: PubMed 33312759Dai H, Tong C, Shi D, Chen M, Guo Y, Chen D, Han X, Wang H, Wang Y, Shen P. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020 Nov 25;9(1):1846926. doi: 10.1080/2162402X.2020.1846926.
- Derived from this study: PubMed 28057014Feng KC, Guo YL, Liu Y, Dai HR, Wang Y, Lv HY, Huang JH, Yang QM, Han WD. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017 Jan 5;10(1):4. doi: 10.1186/s13045-016-0378-7.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti-CD133-CAR vector-transduced T cells in people with Liver Cancer and Pancreatic Cancer, run by Chinese PLA General Hospital at 1 site in China.
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 10 inclusion and 7 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 17 Dec 2019. 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 China. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Occurrence of study related adverse events (time frame: Until week 24). 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 NCT02541370, which also lists 2 linked publications.
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 17 Dec 2019.