Acute Myeloid Leukemia, in RelapsePhase 1NCT04678336
CD123 Redirected T Cells for AML in Pediatric Subjects
A Phase 1 study testing CART123 cells; cyclophosphamide; fludarabine in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia, Pediatric, run by University of Pennsylvania at 1 site in United States.
Trial summary
Phase 1 open-label study to evaluate the safety 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 pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML). Read more about this study
- Who is it for?
- Ages 1 year to 29 years
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, Pediatric, 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
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 2021to 9 May 2025
- 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 1 year to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female patients ≥ 1 and ≤ 29 years of age at time of consent.
- AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically:
- Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR
- Any detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1% (as confirmed by Hematologics); OR
- Refractory disease, defined as persistent bone marrow involvement with >5% blasts after two courses of induction chemotherapy for patients at initial presentation or >5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR.
- Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion.
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- Adequate organ function defined as:
- A serum creatinine based on age/gender
- Adequate liver function
- ALT ≤ 5 x ULN
- Total bilirubin ≤ 3 x ULN
- ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to AML infiltration of the liver.
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
- Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
- Adequate performance status defined as Lansky or Karnofsky score ≥ 50
- Signed informed consent must be obtained.
- No contraindications for leukapheresis (unless apheresis product previously acquired).
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- Pregnant or lactating (nursing) women.
- Patients with relapsed AML with t(15:17).
- Patients < 6 months from alloHSCT.
- HIV infection.
- Active hepatitis B or hepatitis C infection.
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
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- Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroids and immunosuppressant medications (including washout requirements prior to CAR T cell administration).
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- Uncontrolled active infection
- Subjects with CNS3 disease that is progressive on therapy or with CNS parenchymal lesions that may increase the risk of CNS toxicity. Subjects with adequately treated CNS leukemia are eligible.
- Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Patients with any prior history of myeloproliferative neoplasm.
- Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
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 Pediatric Subjects With Refractory or Relapsed Acute Myeloid Leukemia
Phase 1 open-label study to evaluate the safety 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 pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).
Read the detailed description
This is a Phase 1 study designed to evaluate the safety, feasibility, and preliminary efficacy of CART123 cells in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML). The study was originally designed to evaluate these primary endpoints at a single CART123 dose level (2x106 CART123 cells/kg). This dose level was selected based on experience in an adult trial using this investigational product in relapsed/refractory AML patients (NCT03766126).
As of Protocol Amendment V6, the study design has been converted into a 3+3 dose escalation design in order to further explore the safety of CART123 cells in the target disease population, and determine a maximum tolerated dose (MTD). The initial dose level (2x106 CART123 cells/kg) will be retrospectively identified as Dose Level 1 (DL1), and up to two new dose levels of CART123 cells will now be evaluated as follows:
- Dose Level 1 (DL1): 2x106 CART123 cells/kg
- <DL1 Fully Enrolled as of Protocol Amendment V6>
- Dose Level 2 (DL2): 5x106 CART123 cells/kg
- Dose Level 3 (DL3): 1x107 CART123 cells/kg
Dose Level 1 (DL1) was fully evaluated as of Protocol Amendment V6. Dose Level 2 (DL2) and Dose Level 3 (DL3) will be evaluated as follows:
- Dose Level 2 (N = 3-6):
- If 1 DLT/3 subjects occurs, 3 additional DLT-evaluable subjects will enrolled at this dose level.
- If 0 DLT/3 subjects or 1 DLT/6 subjects occur, DL2 safety data will be submitted to the DSMB for review. DSMB approval must be received in order to advance to Dose Level 3 (DL3).
- If 2 DLTs occur at any time, additional enrollment on this study will be paused to allow for further investigation.
- Dose Level 3 (N = 3-6):
- If 1 DLT/3 subjects occurs, 3 additional DLT-evaluable subjects will be enrolled at this dose level.
- If 0 DLT/3 subjects, 3 additional DLT-evaluable subjects will be enrolled at this dose level to further evaluate safety and allow for MTD determination.
- If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If fewer than 6 evaluable subjects were infused at DL2, additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination.
The DLT observation period is 28 days post-CART123 cell infusion (Day 0). In order to allow for appropriate monitoring/assessment of toxicities, study treatment in the 1st and 2nd subjects at each dose level must be staggered by at least 28 days, such that the next subject will not receive treatment (lymphodepleting chemotherapy plus CART123 cells) until the previous subject has completed their Day 28 safety follow-up visit. If there are no emergent safety concerns identified in the first subject infused, study treatment for subsequent subjects at that same dose level do not need to be staggered and may occur sequentially without additional staggering requirements. Formal DLT evaluations will be performed after the 3rd evaluable subject at each dose level reaches the Day 28 safety follow-up visit. These formal DLT evaluations will allow for a formal decision regarding dose level progression, expansion, or dose de-escalation. Formal DLT evaluations will be determined by the Clinical PI and Sponsor Medical Director in accordance with the definition in the protocol. The MTD is defined as the highest dose at which 0 or 1 DLT occurs in 6 evaluable subjects.
It is recommended that subjects with marrow aplasia at Day 28+/-5 undergo an 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 onstudy. All subjects must, therefore, have a previously identified stem cell donor as part of their eligibility to participate in this study. All subjects will be followed monthly for up to 6 months after the 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, Pediatric, 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
CART123 cells following lymphodepleting chemotherapy in pediatric patients with relapsed/refractory AML. Subjects will be treated with a single IV dose of CART123 cells on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | CART123 cells; cyclophosphamide; fludarabine Receives: Biological: CART123 cells; cyclophosphamide; fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety of CART123 in AML subjects
- Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells
- Occurrence of dose-limiting toxicities (DLTs) and determination of Maximum Tolerated Dose (MTD)
Measured: 5 Years
Secondary outcomes (4)
Evaluate study feasibility
- Proportion of enrolled subjects that screen fail; Proportion of enrolled subjects who receive study treatment.
Measured: 15 Years
Evaluate manufacturing feasibility
- Frequency of product release failures; Occurrence of dose failures (inability to meet targeted dose).
Measured: 15 Years
Describe preliminary efficacy
- Reduction of blast count in the peripheral blood and marrow using standard clinical criteria (CBC with differential count, marrow aspirate with differential count) and flow cytometry
- Overall Response Rate (ORR) at 28 +/- 5 days
- Overall survival (OS)
- Progression-free survival (PFS)
- Duration of Response (DOR)
Measured: 15 Years
Evaluate the need for rescue alloHCT
- Percentage of subjects proceeding to alloHCT (or second allogeneic HCT)
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 posted21 Dec 2020
- Study start2 Apr 2021
- Primary completion9 May 2025
- Study completion9 May 2025
Why it stopped: Administrative reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 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
- NCT04678336
- Sponsor's protocol ID
- 834675 (19CT011)
- Status last verified
- Oct 2025
- First submitted
- 22 Oct 2020
- Last updated
- 15 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2025. 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 Pediatric Subjects With Refractory or Relapsed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT04678336
- Acronym / sponsor ID
- 834675 (19CT011)
- Conditions
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, Pediatric, Acute Myeloid Leukemia, Refractory
- Keywords
- refractory, relapsed, Acute, Myeloid, leukemia, AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administrative reasons
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 2 Apr 2021 (actual)
- Primary completion
- 9 May 2025 (actual)
- Study completion
- 9 May 2025 (actual)
- First posted
- 21 Dec 2020 (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 evaluate the safety 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 pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).
Detailed description
This is a Phase 1 study designed to evaluate the safety, feasibility, and preliminary efficacy of CART123 cells in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML). The study was originally designed to evaluate these primary endpoints at a single CART123 dose level (2x106 CART123 cells/kg). This dose level was selected based on experience in an adult trial using this investigational product in relapsed/refractory AML patients (NCT03766126).
As of Protocol Amendment V6, the study design has been converted into a 3+3 dose escalation design in order to further explore the safety of CART123 cells in the target disease population, and determine a maximum tolerated dose (MTD). The initial dose level (2x106 CART123 cells/kg) will be retrospectively identified as Dose Level 1 (DL1), and up to two new dose levels of CART123 cells will now be evaluated as follows:
- Dose Level 1 (DL1): 2x106 CART123 cells/kg
- <DL1 Fully Enrolled as of Protocol Amendment V6>
- Dose Level 2 (DL2): 5x106 CART123 cells/kg
- Dose Level 3 (DL3): 1x107 CART123 cells/kg
Dose Level 1 (DL1) was fully evaluated as of Protocol Amendment V6. Dose Level 2 (DL2) and Dose Level 3 (DL3) will be evaluated as follows:
- Dose Level 2 (N = 3-6):
- If 1 DLT/3 subjects occurs, 3 additional DLT-evaluable subjects will enrolled at this dose level.
- If 0 DLT/3 subjects or 1 DLT/6 subjects occur, DL2 safety data will be submitted to the DSMB for review. DSMB approval must be received in order to advance to Dose Level 3 (DL3).
- If 2 DLTs occur at any time, additional enrollment on this study will be paused to allow for further investigation.
- Dose Level 3 (N = 3-6):
- If 1 DLT/3 subjects occurs, 3 additional DLT-evaluable subjects will be enrolled at this dose level.
- If 0 DLT/3 subjects, 3 additional DLT-evaluable subjects will be enrolled at this dose level to further evaluate safety and allow for MTD determination.
- If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If fewer than 6 evaluable subjects were infused at DL2, additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination.
The DLT observation period is 28 days post-CART123 cell infusion (Day 0). In order to allow for appropriate monitoring/assessment of toxicities, study treatment in the 1st and 2nd subjects at each dose level must be staggered by at least 28 days, such that the next subject will not receive treatment (lymphodepleting chemotherapy plus CART123 cells) until the previous subject has completed their Day 28 safety follow-up visit. If there are no emergent safety concerns identified in the first subject infused, study treatment for subsequent subjects at that same dose level do not need to be staggered and may occur sequentially without additional staggering requirements. Formal DLT evaluations will be performed after the 3rd evaluable subject at each dose level reaches the Day 28 safety follow-up visit. These formal DLT evaluations will allow for a formal decision regarding dose level progression, expansion, or dose de-escalation. Formal DLT evaluations will be determined by the Clinical PI and Sponsor Medical Director in accordance with the definition in the protocol. The MTD is defined as the highest dose at which 0 or 1 DLT occurs in 6 evaluable subjects.
It is recommended that subjects with marrow aplasia at Day 28+/-5 undergo an 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 onstudy. All subjects must, therefore, have a previously identified stem cell donor as part of their eligibility to participate in this study. All subjects will be followed monthly for up to 6 months after the 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Biological: CART123 cells; cyclophosphamide; fludarabineCART123 cells; cyclophosphamide; fludarabine |
Who may qualify
- Ages
- 1 year to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Male and female patients ≥ 1 and ≤ 29 years of age at time of consent.
- AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically:
- Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion.
- Adequate organ function defined as:
- Adequate performance status defined as Lansky or Karnofsky score ≥ 50
Key exclusion criteria (13 listed)
- Pregnant or lactating (nursing) women.
- Patients with relapsed AML with t(15:17).
- Patients < 6 months from alloHSCT.
- HIV infection.
- Active hepatitis B or hepatitis C infection.
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 DomainsCART123 cells following lymphodepleting chemotherapy in pediatric patients with relapsed/refractory AML. Subjects will be treated with a single IV dose of CART123 cells on Day 0. | Biological | Treatment Arm |
Primary outcome
Evaluate the safety of CART123 in AML subjects
Time frame: 5 Years
* Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells * Occurrence of dose-limiting toxicities (DLTs) and determination of Maximum Tolerated Dose (MTD)
4 secondary outcomes
Evaluate study feasibility
Time frame: 15 Years
Evaluate manufacturing feasibility
Time frame: 15 Years
Describe preliminary efficacy
Time frame: 15 Years
Evaluate the need for rescue alloHCT
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 15 Oct 2025.
- 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, Pediatric, 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 18 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 15 Oct 2025. 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?
Evaluate the safety of CART123 in AML subjects (time frame: 5 Years). 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 15 Oct 2025.