Relapsed Adult Myeloid LeukemiaPhase 1/2CART33NCT01864902
Treatment of Relapsed and/or Chemotherapy Refractory CD33 Positive Acute Myeloid Leukemia by CART-33
A Phase 1/2 study testing CART33 cells, anti-CD33 CART and anti-CD33 CAR T cells in people with Relapsed Adult Myeloid Leukemia and Chemotherapy Refractory Adult Myeloid Leukemia, 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 5 to 90 years
- Conditions the study is for
- Relapsed Adult Myeloid Leukemia, Chemotherapy Refractory Adult Myeloid Leukemia
- What is being tested?
- CART33 cells, anti-CD33 CART and anti-CD33 CAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- Apr 2013to Apr 2017
- 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 5 to 90 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 (several months to < 2 year survival) with currently available therapies will be enrolled
- CD33+ acute myeloid leukemia CR can not be achieved after at least 2 prior combination chemotherapy regimens.
- AML in CR(complete remission)2 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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- 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
- Voluntary informed consent is given
Who cannot join
- Pregnant or lactating women
- The safety of this therapy on unborn children is not known
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Uncontrolled active infection
- Active hepatitis B or hepatitis C infection
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
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- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
- Any uncontrolled active medical disorder that would preclude participation as outlined
- HIV infection
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital, Hematological Department, Affiliated Hospital of Changzhi Medical College
Beijing, Beijing Municipality, 100853
Weidong Han, Dr., 86-10-13651392893, hanwdrsw@sina.com
Xuliang Shen, Dr., 86-355-13015365546, shenxlcyp@sohu.com
About this study
Official title: Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
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 to study genetically engineered lymphocyte 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 T cells transduced with the anti-CD33 vector (referred to as CART-33 cells).
II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-leukemia response due to CART-33 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-33 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-33 cells in bone marrow.
IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by CART-33 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD33, and assess correlation with loss of detectable CART-33 (loss of engraftment).
VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 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 13 years.
- Being tested
- CART33 cells, anti-CD33 CART, anti-CD33 CAR T cells
- Keywords
- CD33 positive acute myeloid leukemia (AML)
- Medical subject headings
- Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART33 cellsBiological
Also called chimeric antigen receptor T cells with specificity for CD33
genetically modified lymphocyte therapy
anti-CD33 CARTBiological
Also called CART33
anti-CD33 CAR T cellsBiological
| Study group | Role | What they receive |
|---|---|---|
| anti-CD33 CAR T cells | Experimental | Patients receive anti-CD33-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity. Receives: Biological: CART33 cells; Biological: anti-CD33 CART; Biological: anti-CD33 CAR 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 events) that are possibly, likely, or definitely related to study treatment
Measured: Until week 24
Secondary outcomes (1)
Anti-leukemia responses to CART-33 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 posted30 May 2013 (estimated)
- Study startApr 2013
- Primary completionApr 2016 (estimated)
- Study completionApr 2017 (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 Relapsed Adult Myeloid LeukemiaStudies 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
- 10 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
- NCT01864902
- Sponsor's protocol ID
- CHN-PLAGH-BT-006
- Acronym
- CART33
- Status last verified
- Jan 2016
- First submitted
- 20 May 2013
- Last updated
- 28 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, Wang LL, Han WD. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015 Jan;23(1):184-91. doi: 10.1038/mt.2014.164. Epub 2014 Sep 1.
PubMed 25174587
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
- ClinicalTrials.gov ID
- NCT01864902
- Acronym / sponsor ID
- CART33 / CHN-PLAGH-BT-006
- Keywords
- CD33 positive acute myeloid leukemia (AML)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 30 May 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.
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 to study genetically engineered lymphocyte 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 T cells transduced with the anti-CD33 vector (referred to as CART-33 cells).
II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-leukemia response due to CART-33 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-33 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-33 cells in bone marrow.
IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by CART-33 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD33, and assess correlation with loss of detectable CART-33 (loss of engraftment).
VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 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 13 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-CD33 CAR T cells | Experimental | Biological: CART33 cells, Biological: anti-CD33 CART, Biological: anti-CD33 CAR T cellsPatients receive anti-CD33-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 5 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 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 (several months to < 2 year survival) with currently available therapies will be enrolled
- AML in CR(complete remission)2 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
Key exclusion criteria (10 listed)
- Pregnant or lactating women
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 |
|---|---|---|
| CART33 cellsAlso: chimeric antigen receptor T cells with specificity for CD33genetically modified lymphocyte therapy | Biological | anti-CD33 CAR T cells |
| anti-CD33 CARTAlso: CART33 | Biological | anti-CD33 CAR T cells |
| anti-CD33 CAR T cells | Biological | anti-CD33 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 events) that are possibly, likely, or definitely related to study treatment
1 secondary outcome
Anti-leukemia responses to CART-33 cell infusions
Time frame: up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2016.
- Derived from this study: PubMed 25174587Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, Wang LL, Han WD. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015 Jan;23(1):184-91. doi: 10.1038/mt.2014.164. Epub 2014 Sep 1.
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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 CART33 cells, anti-CD33 CART and anti-CD33 CAR T cells in people with Relapsed Adult Myeloid Leukemia and Chemotherapy Refractory Adult Myeloid Leukemia, 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 13 inclusion and 10 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 28 Jan 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 Weidong Han, Dr. (86-10-13651392893, hanwdrsw@sina.com), or a site near the patient. 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 NCT01864902, 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 28 Jan 2016.