Acute Myeloid LeukemiaPhase 1NCT05672147
CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia
A Phase 1 study testing Anti-CD33 CAR T-cells and Lymphodepletion Therapy in people with Acute Myeloid Leukemia and Recurrent Adult Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.
Trial summary
This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Anti-CD33 CAR T-cells and Lymphodepletion Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2023to 3 Sep 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening, while the request for a translated full consent is processed
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with Study principal investigator (PI) approval
- Age: >= 18 years
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- Karnofsky Performance Scale (KPS) >= 70
- Life expectancy >= 16 weeks at the time of enrollment
- Prior allogeneic transplant allowed if > 6 months prior to study enrollment
- Participant must have a confirmed diagnosis of active CD33+ AML de novo, or secondary OR participants who are at a high risk for disease recurrence
- Relapsed AML is defined as patients that had a first complete response (CR) before developing recurrent disease (increased bone marrow blasts)
- Refractory AML is defined as patients that have not achieved a first CR after induction chemotherapy. For patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy
- Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML
- CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry. Cytogenetics, flow cytometry, and molecular studies (such as FLT-3 status) will be obtained as per standard practice
- Research participants who are at a high risk of disease recurrence, they must have historical bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML
- No known contraindications to lymphodepleting agents, steroids, tocilizumab and/or cetuximab, or the investigational agent
- Total serum bilirubin =< 2.0 mg/dL
- Participants with Gilbert syndrome may be included if their total bilirubin is =< 3.0
- Aspartate aminotransferase (AST) =< 3 x the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) =< 3 x ULN
- Estimated creatinine clearance of >= 60 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis
- Left ventricular ejection fraction >= 50% within 8 weeks before enrollment
- Oxygen (O2) saturation > 92% not requiring oxygen supplementation
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
- Research participants must have a potential donor or stem cell source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical)
- DONOR: The identified donor must be the original donor whose stem cells were used for the research participant's allogeneic hematopoietic stem cell transplantation (alloSCT)
- DONOR: The donor must be HIV negative
- DONOR: KPS >= 70
- DONOR: Documented body weight
Who cannot join
- Prior allogeneic transplant if < 6 months prior to enrollment
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications should be stopped 28-days prior to enrollment. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg/day, or equivalent doses of other corticosteroids) is allowed
- Participants with active autoimmune disease, including graft versus host disease (GvHD), requiring systemic immune suppressive should be stopped 28-days prior to enrollment
- Participants may not be receiving any other investigational agents and are not dependent on concurrent biological therapy, chemotherapy, or radiation therapy
- With exception to Hydrea which must be stopped prior to initiation of lymphodepletion
- Research participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. However, participants on antifungal prophylaxis are eligible
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- Not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
- Subjects with >= Grade 2 myelofibrosis on bone marrow biopsy
- Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening if the patient is undergoing leukapheresis. Patients with controlled atrial arrythmia is allowed
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to screening
- Subjects with presence of other active malignancy, however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
- Clinically significant uncontrolled illness
- Active infection requiring antibiotics
- Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection based on testing performed within 4 weeks of enrollment
- Active viral hepatitis
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Karamjeet S. Sandhu, 626-218-2405, ksandhu@coh.org
Karamjeet S. Sandhu
About this study
Official title: Phase I Study of Cellular Immunotherapy Using T Cells Lentivirally Transduced to Express a Cd33-Specific Chimeric Antigen Receptor for Patients With Cd33+ Relapsed/Refractory Acute Myeloid Leukemia
This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient or donor's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's or donor's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.
Read the detailed description
PRIMARY OBJECTIVE:
- Examine the anti-tumor activity and safety of administering patient-specific donor-derived (allogeneic) CD33-CAR T cells following lymphodepletion in research participants with CD33+ recurrent/refractory (r/r) acute myeloid leukemia (AML).
SECONDARY OBJECTIVE:
- Assess activity in the form of CAR T cell expansion and persistence, to assess impact on hematopoiesis, 6-month progression free survival (PFS 6mo) rate, duration of response, and 1-year overall survival (OS) rate.
EXPLORATORY OBJECTIVES:
- Change from baseline in numbers of CD33+ blood cells, CD33 expression on leukemia cells and hematopoietic cells.
II. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred CD33R(CD8h)BBzeta/EGFRt+ T cells.
OUTLINE: This is a dose-escalation study.
Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells intravenously (IV) on day 0. Patients with persistent CD33+ AML who are > 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.
- Conditions
- Acute Myeloid Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia
- Being tested
- Anti-CD33 CAR T-cells, Lymphodepletion Therapy
- 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 T-cellsBiological
Also called Anti-CD33 CAR T Cells, Anti-CD33 CAR-T Cells, CD33-CAR T Cells
Given IV
Lymphodepletion TherapyProcedure or surgery
Also called Lymphodepleting Therapy, Lymphodepletion
Undergo lymphodepletion
| Study group | Role | What they receive |
|---|---|---|
| Treatment (anti-CD33 CAR T-cells) | Experimental | Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells IV on day 0. Patients with persistent CD33+ AML who are > 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV. Receives: Biological: Anti-CD33 CAR T-cells; Procedure: Lymphodepletion Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants who achieve measurable residual disease (MRD)
Defined as complete response (CR) or MRD- complete response with incomplete hematopoietic recovery. Rates and associated 90% Clopper and Pearson binomial confidence limits.
Measured: Up to 15 years post study treatment
Incidence of dose-limiting toxicities and full toxicity profile
Rates and associated 90% toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0, and modified Cytokine Release Syndrome grading as applicable. Clopper and Pearson binomial confidence limits.
Measured: Up to 1 year following the last CAR T cell infusion
Secondary outcomes (5)
Expansion and persistence of the CAR T cell product
Descriptive statistics and graphical methods will be used to present expansion and persistence.
Measured: Up to 15 years post-CAR T cell infusion
Percent and counts from peripheral blood cell subsets in hematopoietic stem/progenitor cell compartments
Descriptive statistics and graphical methods will be used to present T cell numbers and percentages over time.
Measured: Up to 15 years post-CAR T cell infusion
Duration of response
Patients who have not had disease relapse/progression or death at the last follow-up will be censored at the time of last follow-up. Patients who never achieved CR will be excluded from the analysis. Descriptive statistics will be provided for duration of response.
Measured: From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years post CAR T cell infusion
Progression-free survival
Participants are considered a failure for this endpoint if they die (regardless of cause) or experience disease relapse.
Measured: From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years post CAR T cell infusion
Overall survival
Participants are considered a failure for this endpoint if they die, regardless of cause.
Measured: from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years post CAR T cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2023
- Study start7 Dec 2023
- Primary completion3 Sep 2028 (estimated)
- Study completion3 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical 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
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Karamjeet S Sandhu, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05672147
- Sponsor's protocol ID
- 21665
- Other IDs
- NCI-2022-10310, 21665, P30CA033572
- Status last verified
- Mar 2026
- First submitted
- 3 Jan 2023
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Cellular Immunotherapy Using T Cells Lentivirally Transduced to Express a Cd33-Specific Chimeric Antigen Receptor for Patients With Cd33+ Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05672147
- Acronym / sponsor ID
- 21665
- Conditions
- Acute Myeloid Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Dec 2023 (actual)
- Primary completion
- 3 Sep 2028 (estimated)
- Study completion
- 3 Sep 2028 (estimated)
- First posted
- 5 Jan 2023 (actual)
- 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 tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient or donor's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's or donor's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.
Detailed description
PRIMARY OBJECTIVE:
- Examine the anti-tumor activity and safety of administering patient-specific donor-derived (allogeneic) CD33-CAR T cells following lymphodepletion in research participants with CD33+ recurrent/refractory (r/r) acute myeloid leukemia (AML).
SECONDARY OBJECTIVE:
- Assess activity in the form of CAR T cell expansion and persistence, to assess impact on hematopoiesis, 6-month progression free survival (PFS 6mo) rate, duration of response, and 1-year overall survival (OS) rate.
EXPLORATORY OBJECTIVES:
- Change from baseline in numbers of CD33+ blood cells, CD33 expression on leukemia cells and hematopoietic cells.
II. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred CD33R(CD8h)BBzeta/EGFRt+ T cells.
OUTLINE: This is a dose-escalation study.
Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells intravenously (IV) on day 0. Patients with persistent CD33+ AML who are > 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (anti-CD33 CAR T-cells) | Experimental | Biological: Anti-CD33 CAR T-cells, Procedure: Lymphodepletion TherapyPatients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells IV on day 0. Patients with persistent CD33+ AML who are > 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Documented informed consent of the participant and/or legally authorized representative
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- Age: >= 18 years
- Karnofsky Performance Scale (KPS) >= 70
- Life expectancy >= 16 weeks at the time of enrollment
Key exclusion criteria (19 listed)
- Prior allogeneic transplant if < 6 months prior to enrollment
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications should be stopped 28-days prior to enrollment. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg/day, or equivalent doses of other corticosteroids) is allowed
- Participants with active autoimmune disease, including graft versus host disease (GvHD), requiring systemic immune suppressive should be stopped 28-days prior to enrollment
- Participants may not be receiving any other investigational agents and are not dependent on concurrent biological therapy, chemotherapy, or radiation therapy
- Research participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. However, participants on antifungal prophylaxis are eligible
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 T-cellsAlso: Anti-CD33 CAR T Cells, Anti-CD33 CAR-T Cells, CD33-CAR T CellsGiven IV | Biological | Treatment (anti-CD33 CAR T-cells) |
| Lymphodepletion TherapyAlso: Lymphodepleting Therapy, LymphodepletionUndergo lymphodepletion | Procedure or surgery | Treatment (anti-CD33 CAR T-cells) |
Primary outcome
Participants who achieve measurable residual disease (MRD)
Time frame: Up to 15 years post study treatment
Defined as complete response (CR) or MRD- complete response with incomplete hematopoietic recovery. Rates and associated 90% Clopper and Pearson binomial confidence limits.
Incidence of dose-limiting toxicities and full toxicity profile
Time frame: Up to 1 year following the last CAR T cell infusion
Rates and associated 90% toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0, and modified Cytokine Release Syndrome grading as applicable. Clopper and Pearson binomial confidence limits.
5 secondary outcomes
Expansion and persistence of the CAR T cell product
Time frame: Up to 15 years post-CAR T cell infusion
Percent and counts from peripheral blood cell subsets in hematopoietic stem/progenitor cell compartments
Time frame: Up to 15 years post-CAR T cell infusion
Duration of response
Time frame: From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years post CAR T cell infusion
Progression-free survival
Time frame: From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years post CAR T cell infusion
Overall survival
Time frame: from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years post CAR T cell infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
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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.
Karamjeet S Sandhu principal investigator
City of Hope 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 Anti-CD33 CAR T-cells and Lymphodepletion Therapy in people with Acute Myeloid Leukemia and Recurrent Adult Acute Myeloid Leukemia, run by City of Hope 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 32 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 5 Mar 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants who achieve measurable residual disease (MRD) (time frame: Up to 15 years post study treatment). The study lists 2 primary outcomes in all. 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 5 Mar 2026.