Acute Myelogenous LeukemiaPhase 1/2NCT02944162
CAR-pNK Cell Immunotherapy for Relapsed/Refractory CD33+ AML
A Phase 1/2 study testing anti-CD33 CAR-NK cells in people with Acute Myelogenous Leukemia and Acute Myeloid Leukemia, run by PersonGen BioTherapeutics (Suzhou) Co., Ltd. at 1 site in China.
Trial summary
The purpose of this clinical trial is to study genetically engineered NK92 cell therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy. Read more about this study
- Who is it for?
- Ages 3 to 80 years
- Conditions the study is for
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With Maturation
- What is being tested?
- anti-CD33 CAR-NK cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- Oct 2016to Sep 2018
- 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 3 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (>12 weeks to < 2 year survival) with currently available therapies will be enrolled.
- CD33+ acute myeloid leukemia CR (complete remission) can not be achieved after at least 2 prior combination chemotherapy regimens.
- AML in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
- Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
- Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
- Residual disease after primary therapy and not eligible for autologous SCT.
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- All of those patients must also meet the following criteria:
- Expected survival > 12 weeks. Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior SCT will make patient eligible regardless of other prior therapy.
- Adequate venous access for apheresis, and no other contraindications for leukapheresis.
- Ability to give informed consent.
Who cannot join
- Pregnant or nursing women may not participate.
- Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.
- Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
- History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- The existence of unstable or active ulcers or gastrointestinal bleeding.
- Patients need anticoagulant therapy (such as warfarin or heparin).
- Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Suzhou, Jiangsu, 215123
Lin Yang, Ph.D, 86-512-65922190, info@persongen.com
Yangyi Bao, MD
About this study
Official title: Clinical Investigation of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified NK92 Cells in Relapsed and/or Refractory Acute Myeloid Leukemias
The purpose of this clinical trial is to study genetically engineered NK92 cell therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.
Read the detailed description
PRIMARY OBJECTIVES:
Determine the safety and feasibility of the chimeric antigen receptor NK92 cells transduced with the anti-CD33 vector (referred to as anti-CD33 CAR-NK cells).
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-leukemia response due to anti-CD33 CAR-NK cell infusions.
II. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by anti-CD33 CAR-NK in vitro.
III. Determine if cellular or humoral host immunity develops against the murine anti-CD33.
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33 CAR-NK (coupled with CD28, CD137 and CD3 zeta signalling domains) vector-transduced NK92 cell line on days 0,3, and 5 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.
- Conditions
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With Maturation, Acute Myeloid Leukemia Without Maturation, ANLL
- Being tested
- anti-CD33 CAR-NK cells
- Keywords
- AML, CD33, CAR-NK
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD33 CAR-NK cellsBiological
Also called Chimeric antigen receptor NK92 cells with specificity for CD33
The allogeneic NK cells (NK-92 cell line for clinical use) are engineered to contain anti-CD33 attached to TCRzeta, CD28 and 4-1BB signaling domains. These modified cells are called chimeric antigen receptor NK cells with specificity for CD33.
| Study group | Role | What they receive |
|---|---|---|
| CAR-NK Cell immunotherapy | Experimental | Enrolled patients will receive CAR-NK cells immunotherapy with a novel specific chimeric antigen receptor targeting CD33 antigen by infusion. Receives: Biological: anti-CD33 CAR-NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events attributed to the administration of the anti-CD33 CAR-NK cells
Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment
Measured: One year
Secondary outcomes (1)
Objective Response Rate
Anti-leukemia responses to anti-CD33 CAR-NK cell infusions
Measured: Up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2016 (estimated)
- Study startOct 2016
- Primary completionSep 2017 (estimated)
- Study completionSep 2018 (estimated)
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 Acute Myelogenous LeukemiaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PersonGen BioTherapeutics (Suzhou) Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The First People's Hospital of Hefei, Hefei Binhu Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02944162
- Sponsor's protocol ID
- PG-0332
- Status last verified
- Oct 2016
- First submitted
- 23 Oct 2016
- Last updated
- 6 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: (1) The use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (2) Seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (3) Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD.
Publications
Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.
PubMed 28054442
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Investigation of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified NK92 Cells in Relapsed and/or Refractory Acute Myeloid Leukemias
- ClinicalTrials.gov ID
- NCT02944162
- Acronym / sponsor ID
- PG-0332
- Conditions
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With Maturation, Acute Myeloid Leukemia Without Maturation, ANLL
- Keywords
- AML, CD33, CAR-NK
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- PersonGen BioTherapeutics (Suzhou) Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- The First People's Hospital of Hefei, Hefei Binhu Hospital
- Study start
- Oct 2016
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 25 Oct 2016 (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.
The purpose of this clinical trial is to study genetically engineered NK92 cell therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.
Detailed description
PRIMARY OBJECTIVES:
Determine the safety and feasibility of the chimeric antigen receptor NK92 cells transduced with the anti-CD33 vector (referred to as anti-CD33 CAR-NK cells).
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-leukemia response due to anti-CD33 CAR-NK cell infusions.
II. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by anti-CD33 CAR-NK in vitro.
III. Determine if cellular or humoral host immunity develops against the murine anti-CD33.
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33 CAR-NK (coupled with CD28, CD137 and CD3 zeta signalling domains) vector-transduced NK92 cell line on days 0,3, and 5 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-NK Cell immunotherapy | Experimental | Biological: anti-CD33 CAR-NK cellsEnrolled patients will receive CAR-NK cells immunotherapy with a novel specific chimeric antigen receptor targeting CD33 antigen by infusion. |
Who may qualify
- Ages
- 3 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (>12 weeks to < 2 year survival) with currently available therapies will be enrolled.
- CD33+ acute myeloid leukemia CR (complete remission) can not be achieved after at least 2 prior combination chemotherapy regimens.
- AML in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
- Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
- Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
Key exclusion criteria (8 listed)
- Pregnant or nursing women may not participate.
- Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.
- Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
- History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
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-CD33 CAR-NK cellsAlso: Chimeric antigen receptor NK92 cells with specificity for CD33The allogeneic NK cells (NK-92 cell line for clinical use) are engineered to contain anti-CD33 attached to TCRzeta, CD28 and 4-1BB signaling domains. These modified cells are called chimeric antigen receptor NK cells with specificity for CD33. | Biological | CAR-NK Cell immunotherapy |
Primary outcome
Adverse events attributed to the administration of the anti-CD33 CAR-NK cells
Time frame: One year
Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment
1 secondary outcome
Objective Response Rate
Time frame: Up to one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2016.
- Derived from this study: PubMed 28054442Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.
- Individual participant dataSharing planned: Yes. (1) The use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (2) Seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (3) Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD.
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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.
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-CD33 CAR-NK cells in people with Acute Myelogenous Leukemia and Acute Myeloid Leukemia, run by PersonGen BioTherapeutics (Suzhou) Co., Ltd. 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 8 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: status not confirmed, as of the sponsor's last update on 6 Dec 2016. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lin Yang, Ph.D (86-512-65922190, info@persongen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events attributed to the administration of the anti-CD33 CAR-NK cells (time frame: One year). 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 NCT02944162, 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 6 Dec 2016.