Acute Myeloid Leukemia, in RelapsePhase 1NCT03766126
Lentivirally Redirected CD123 Autologous T Cells in AML
A Phase 1 study testing CART123 cells; cyclophosphamide; fludarabine in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia, Adult, run by University of Pennsylvania at 1 site in United States.
Trial summary
Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in Acute Myeloid Leukemia (AML) subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, Adult, Acute Myeloid Leukemia, Refractory
- What is being tested?
- CART123 cells; cyclophosphamide; fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2018to 5 Mar 2026
- 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
- Male or female subjects 18 years of age or older
- Subjects with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. Specifically:
- AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria (Döhner et al., 2017 Blood, 129(4):424-447); partial remission or refractory disease (including primary refractory) are eligible. Or:
- AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible
- Subjects with relapsed disease after prior transplant must meet one of the following:
- Subjects with relapsed disease after prior allogeneic HCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and i. Have no residual donor cells (by STR analysis on 2 occasions separated by at least 1 month), OR: ii. Donor cells are present but there is no active GVHD (>Gr II), subject does not require systemic immunosuppression and is more than 3 months from transplant, and at least 1 month off GVHD prophylaxis.
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- Subjects with relapsed disease after prior autologous or syngeneic HCT will be eligible if they meet all other inclusion criteria and it has been more than 3 months from transplant.
- Subjects must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
- Satisfactory organ functions:
- Creatinine ≤ 1.6 mg/dl
- ALT/AST must be ≤5 x upper limit of normal unless related to disease
- Direct bilirubin or total bilirubin < 2.0mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL);
- Left ventricular ejection fraction ≥ 40% as confirmed by ECHO/MUGA
- ECOG Performance status 0-2.
- Written informed consent is given.
- No contraindications for leukapheresis.
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- Pregnant or lactating (nursing women) women.
- Patients with relapsed AML with t(15:17).
- HIV infection.
- Active hepatitis B or hepatitis C infection.
- Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. For additional details regarding use of steroids while on study.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
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- Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
- Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
- Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the Screening/Enrollment visit.
- Patients with any prior history of myeloproliferative neoplasm.
- Patients with the JAK2 V617F mutation by PCR or next generation sequencing.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Refractory or Relapsed Acute Myeloid Leukemia
Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in Acute Myeloid Leukemia (AML) subjects.
Read the detailed description
This is a Phase 1 study to determine the safety, feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with a split dosing approach of CART123 cells (10% Day 0; 30% Day 1; 60% Day 2) for Cohort 1a/1b or a single IV administration of CART123 cells for Cohort 2.
The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose, preceded by lymphodepleting chemotherapy, is 1-2x10^6 CART123 cells/kg for Cohort 1a, 5x10^6 CART123 cells/kg for Cohort 1b, or 2x10^6 CART-123 cells/kg for Cohort 2. The protocol-specified minimum acceptable dose for infusion is 1x10^5 CART123 cells/kg for all cohorts.
It is recommended per routine clinical care, that all subjects with marrow aplasia at Day 28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study, however subjects will continue to be followed on study. All subjects should therefore have a previously identified stem cell donor in order to participate in this study. Please see Section 6.8 for additional details.
All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion (Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.
- Conditions
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, Adult, Acute Myeloid Leukemia, Refractory
- Being tested
- CART123 cells; cyclophosphamide; fludarabine
- Keywords
- refractory, relapsed, Acute, Myeloid, leukemia, AML
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART123 cells; cyclophosphamide; fludarabineBiological
Also called T Cells Containing Anti-CD123 Signaling Domains
The total dose administered to each subject will be based on body weight obtained at the time of apheresis.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1a subjects | Experimental | CART123 cells via IV infusion at a dose of 1-2x106 CART123 cells/kg using a split dosing approach (10% Day 0; 30% Day 1; 60% Day 2), following lymphodepleting chemotherapy. Receives: Biological: CART123 cells; cyclophosphamide; fludarabine |
| Cohort 1b subjects | Experimental | CART123 cells via IV infusion at a dose of 5x106 CART123 cells/kg using a split dosing approach (10% Day 0; 30% Day 1; 60% Day 2), following lymphodepleting chemotherapy. Receives: Biological: CART123 cells; cyclophosphamide; fludarabine |
| Cohort 2 subjects | Experimental | CART123 cells via a single IV infusion at a dose of 2x106 CART123 cells/kg, following lymphodepleting chemotherapy. Receives: Biological: CART123 cells; cyclophosphamide; fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile of CART123 cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute (NCI) - Common Toxicity Criteria (v5.0)
Measured: 15 years
Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.
Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.
Measured: 1 year
Secondary outcomes (5)
Estimation of CART123 efficacy by evaluation of OS and PFS of subjects at protocol defined intervals which receive at least one infusion of CART123 cells
Estimate the efficacy of at least 1 dose of CART123 cells in AML subjects
Measured: 15 years
Overall Survival (OS) as percent of subjects surviving at protocol defined time points.
Overall survival (OS) and progression-free survival (PFS)
Measured: 15 years
Progression-free survival (PFS) as percent of subjects surviving without disease progression at protocol defined time points
Measured: 15 years
Duration of response (DOR)
Duration of response (DOR)
Measured: 15 years
Necessity of rescue bone marrow transplant
Need for rescue allogeneic hematopoietic cell transplantation (alloHCT)
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2018
- Study start6 Dec 2018
- Primary completion5 Mar 2026
- Study completion5 Mar 2026
Why it stopped: Administrative reasons.
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 Myeloid Leukemia, in RelapseStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03766126
- Sponsor's protocol ID
- 831619 (UPCC 35418)
- Status last verified
- Jul 2026
- First submitted
- 3 Dec 2018
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bhagwat AS, Torres L, Shestova O, Shestov M, Mellors PW, Fisher HR, Farooki SN, Frost BF, Loken MR, Gaymon AL, Frazee D, Rogal W, Frey N, Hexner EO, Luger SM, Loren AW, Martin ME, McCurdy SR, Perl AE, Stadtmauer EA, Brogdon JL, Fraietta JA, Hwang WT, Siegel DL, Plesa G, Aplenc R, Porter DL, June CH, Gill SI. Cytokine-mediated CAR T therapy resistance in AML. Nat Med. 2024 Dec;30(12):3697-3708. doi: 10.1038/s41591-024-03271-5. Epub 2024 Sep 27.
PubMed 39333315
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Refractory or Relapsed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03766126
- Acronym / sponsor ID
- 831619 (UPCC 35418)
- Conditions
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, Adult, Acute Myeloid Leukemia, Refractory
- Keywords
- refractory, relapsed, Acute, Myeloid, leukemia, AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administrative reasons.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 5 Mar 2026 (actual)
- Study completion
- 5 Mar 2026 (actual)
- First posted
- 6 Dec 2018 (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.
Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in Acute Myeloid Leukemia (AML) subjects.
Detailed description
This is a Phase 1 study to determine the safety, feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with a split dosing approach of CART123 cells (10% Day 0; 30% Day 1; 60% Day 2) for Cohort 1a/1b or a single IV administration of CART123 cells for Cohort 2.
The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose, preceded by lymphodepleting chemotherapy, is 1-2x10^6 CART123 cells/kg for Cohort 1a, 5x10^6 CART123 cells/kg for Cohort 1b, or 2x10^6 CART-123 cells/kg for Cohort 2. The protocol-specified minimum acceptable dose for infusion is 1x10^5 CART123 cells/kg for all cohorts.
It is recommended per routine clinical care, that all subjects with marrow aplasia at Day 28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study, however subjects will continue to be followed on study. All subjects should therefore have a previously identified stem cell donor in order to participate in this study. Please see Section 6.8 for additional details.
All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion (Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1a subjects | Experimental | Biological: CART123 cells; cyclophosphamide; fludarabineCART123 cells via IV infusion at a dose of 1-2x106 CART123 cells/kg using a split dosing approach (10% Day 0; 30% Day 1; 60% Day 2), following lymphodepleting chemotherapy. |
| Cohort 1b subjects | Experimental | Biological: CART123 cells; cyclophosphamide; fludarabineCART123 cells via IV infusion at a dose of 5x106 CART123 cells/kg using a split dosing approach (10% Day 0; 30% Day 1; 60% Day 2), following lymphodepleting chemotherapy. |
| Cohort 2 subjects | Experimental | Biological: CART123 cells; cyclophosphamide; fludarabineCART123 cells via a single IV infusion at a dose of 2x106 CART123 cells/kg, following lymphodepleting chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female subjects 18 years of age or older
- Subjects with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. Specifically:
- Subjects with relapsed disease after prior transplant must meet one of the following:
- Subjects must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
- Satisfactory organ functions:
Key exclusion criteria (13 listed)
- Pregnant or lactating (nursing women) women.
- Patients with relapsed AML with t(15:17).
- HIV infection.
- Active hepatitis B or hepatitis C infection.
- Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. For additional details regarding use of steroids while on 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 |
|---|---|---|
| CART123 cells; cyclophosphamide; fludarabineAlso: T Cells Containing Anti-CD123 Signaling DomainsThe total dose administered to each subject will be based on body weight obtained at the time of apheresis. | Biological | Cohort 1a subjects, Cohort 1b subjects, Cohort 2 subjects |
Primary outcome
Safety profile of CART123 cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute (NCI) - Common Toxicity Criteria (v5.0)
Time frame: 15 years
Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.
Time frame: 1 year
Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.
5 secondary outcomes
Estimation of CART123 efficacy by evaluation of OS and PFS of subjects at protocol defined intervals which receive at least one infusion of CART123 cells
Time frame: 15 years
Overall Survival (OS) as percent of subjects surviving at protocol defined time points.
Time frame: 15 years
Progression-free survival (PFS) as percent of subjects surviving without disease progression at protocol defined time points
Time frame: 15 years
Duration of response (DOR)
Time frame: 15 years
Necessity of rescue bone marrow transplant
Time frame: 15 years
Results and safety
The study was stopped early (reason given: Administrative reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Derived from this study: PubMed 39333315Bhagwat AS, Torres L, Shestova O, Shestov M, Mellors PW, Fisher HR, Farooki SN, Frost BF, Loken MR, Gaymon AL, Frazee D, Rogal W, Frey N, Hexner EO, Luger SM, Loren AW, Martin ME, McCurdy SR, Perl AE, Stadtmauer EA, Brogdon JL, Fraietta JA, Hwang WT, Siegel DL, Plesa G, Aplenc R, Porter DL, June CH, Gill SI. Cytokine-mediated CAR T therapy resistance in AML. Nat Med. 2024 Dec;30(12):3697-3708. doi: 10.1038/s41591-024-03271-5. Epub 2024 Sep 27.
- Individual participant dataSharing planned: No
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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 study testing CART123 cells; cyclophosphamide; fludarabine in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia, Adult, run by University of Pennsylvania 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 17 inclusion and 13 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 10 Jul 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?
The study was stopped early (reason given: Administrative reasons.). 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?
Safety profile of CART123 cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute (NCI) - Common Toxicity Criteria (v5.0) (time frame: 15 years). 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?
On the ClinicalTrials.gov record for NCT03766126, 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 10 Jul 2026.