Refractory Acute Myeloid LeukemiaPhase 1NCT06017258
A Study of CD371-YSNVZIL-18 CAR T Cells in People With Acute Myeloid Leukemia
A Phase 1 study testing CD371-specific/YSNVz/I-18 CAR T cells in people with Refractory Acute Myeloid Leukemia and Relapsed Acute Myeloid Leukemia, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to find out whether CD371-YSNVZ-IL18 CAR T cells are safe, and to look for the highest dose of CD371-YSNVZ-IL18 CAR T cells that cause few or mild side effects in participants. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Myeloid Leukemia
- What is being tested?
- CD371-specific/YSNVz/I-18 CAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 7 sitesUnited States
- Study dates
- 1 Sep 2023to 17 Dec 2027
- Phase
- Phase 1
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 and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subject Inclusion: Collection of T cells (Part A)
- History of CD371+ AML
- Any disease status is eligible for collection
- Expression of CD371 at any level on AML blasts (any method of detection including IHC and/or flow cytometry)
- Age/Weight
- Pediatrics: ≥ 1 year and ≥ 10kg for collection for dose levels, 1, 2, and -1
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- ≥ 12 years and ≥ 40 kg for collection for dose level 1A.
- Adults: no limit on age/weight for collection for dose levels 1, 2, and -1.
- ≥ 40 kg for collection for dose level 1A.
- Patients with history of allo-HCT are eligible for collection if:
- ≥ 100 days post-transplant however, as noted in Section 6.1.2, patients must be ≥180 days post-transplant to be eligible for treatment
- no evidence of active GVHD
- off any immunosuppressive agents for 30 days prior to collection (physiologic dose of corticosteroids is acceptable)
- Subject Inclusion: Treatment with CD371-specific/YSNVz/IL-18 CAR T cells (Part B)
- Relapsed/Refractory CD371+ AML (meeting criteria defined below) for primary refractory AML, late first relapse, and/or advanced disease:
- o Primary refractory AML: Patients are eligible from disease perspective in the event of failure to achieve a CR, CRh or CRi after one or more of the following regimens:
- Two or more courses of standard intensive induction chemotherapy (e.g., cytarabine and daunorubicin given as "7+3," MEC, HiDAC, FLAG+idarubicin, etc.);
- Two or more cycles of venetoclax in combination with one of the following (azacitidine OR decitabine OR low-dose cytarabine), with or without other agents;
- Six or more cycles of azacitidine monotherapy OR four or more courses of decitabine monotherapy
- Early first relapse: Patients are eligible from disease perspective in the event of first morphologic relapse or new extramedullary disease less than 12 months after previously having achieved CR, CRh, or CRi following AML-directed therapy
- Late first relapse: Patients with first morphologic relapse or new extramedullary disease ≥12 months after previously having achieved CR, CRh, or CRi following AML-directed therapy may respond to intensive re-induction using the initial induction regimen and not eligible from a disease perspective unless the treating investigator feels the patient is unlikely to benefit from repeating the initial induction regimen (for example, relapse occurring 12 months into CR on continuous azacitidine/venetoclax therapy), in which case the rationale for considering enrollment must be clearly documented and risks, benefits, and alternatives discussed with the patient.
- Advanced disease: Patients are eligible from disease perspective in the event of relapsed AML refractory to reinduction therapy, relapse following alloHCT, or second or later relapse.
- Disease eligibility considerations for all patients: Patients with relapsed or refractory AML with susceptible mutations for which there is an FDA approved therapy (for example, IDH1 mutation, ivosidenib; IDH2 mutation, enasidenib; FLT3-ITD/TKD, gilteritinib) are not eligible from a disease perspective unless they meet one or more of the below criteria:
- Failure to achieve CR, CRh, or CRi following therapy with one or more targeted therapies for relapsed or refractory AML directed to the actionable mutation(s);
- Intolerance of one or more targeted therapies for relapsed or refractory AML directed to the actionable mutation(s);
- Treating investigator feels the patient would be unlikely to benefit from FDA-approved targeted therapy based on disease characteristics, in which case the rationale for considering enrollment must be clearly documented and risks, benefits, and alternatives discussed with the patient Age: any age is eligible for treatment if eligible for collection
- o The first 3 patients in the first dose cohort must be ≥ 16 years of age, while the first 2 patients in subsequent cohorts must be ≥ 16 years of age (see Section 10.4) . Nopatient enrolled to dose level 1A shall be <12 years of age (and first 2 patients must be ≥ 16 years of age).
- Adequate performance status:
- Age ≥ 16 years: ECOG ≤ 1 or Karnosfsky ≥ 60
- Age < 16 years: Lansky ≥ 60
- Patients with history of allo-HCT are eligible for treatment if:
- ≥ 180 days post-transplant
- no evidence of active GVHD
- off any systemic immunosuppressive agents for 30 days prior to treatment (physiologic dose of corticosteroids is acceptable)
- Treating physician considers the patient to be a candidate for second alloHCT
- Identification of a suitable donor/source for alloHCT as determined by the treating physician.
- Adequate organ function is required, defined as follows:
- Hepatic: Serum total bilirubin ≤ 1.5 mg/dL, unless benign congenital hyperbilirubinemia or unless thought to be disease related.
- Hepatic: ALT and AST < 3 times the upper limit of normal unless thought to be disease-related.
- Renal: serum creatinine < 2.0 mg/100 ml (> 18 years) or ≤ 2.5 x institutional upper limit of normal (ULN) for age
- If serum creatinine is outside the normal range, then CrCl > 40 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.73m2) > 40% of predicted normal for age.
- Normal GFR by Age Age: 1 week / Mean GFR +/-SD (mL/min/1.73 m2): 40.6 + / - 14.8 Age: 2 - 8 weeks / Mean GFR +/-SD (mL/min/1.73 m2): 65.8 + / - 24.8 Age: > 8 weeks / Mean GFR +/-SD (mL/min/1.73 m2): 95.7 +/- 21.7 Age: 2 - 12 years / Mean GFR +/-SD (mL/min/1.73 m2): 133 +/- 27 Age: 13 - 21 years (males) / Mean GFR +/-SD (mL/min/1.73 m2): 140 +/- 30 Age: 13 - 21 years (females) / Mean GFR +/-SD (mL/min/1.73 m2): 126.0 + / - 22.0 Abbreviations: GFR, glomerular f filtration rate; SD, standard deviation
- Greater than 2 years old: Normal GFR is 100 mL/min/1.73m2.
- Infants: GFR must be corrected for body surface area.
- Cardiac: LVEF ≥ 50% by MUGA or resting echocardiogram.
- Pulmonary: Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by pulse oximetry
Who cannot join
- Subject Exclusion: Collection of T cells (Part A)
- Pregnant or lactating women; women of childbearing age, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception while receiving study treatment and for at least 12 months after all treatment is finished
- Sexually active males, unless they are willing to use a condom during intercourse while receiving study treatment and for at least 12 months after all treatment is finished
- Radiographically-detected or symptomatic CNS disease or CNS 3 disease (i.e., presence of ≥ 5/ul WBC in CSF). Subjects with adequately treated CNS leukemia are eligible.
- Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject
- Impaired cardiac function (LVEF < 50%) as assessed by ECHO or MUGA scan
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- Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction ≤ 6 months prior to enrollment
- History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- Positive serologic test results for HIV
- Acute or chronic HBV infection as assessed by serologic (HBVsAg) or PCR results, defined as HBVsAg+, HBVcAb+, HBV PCR+.
- Acute or chronic HCV infection as assessed by serologic (HCV ab) or PCR results, defined as HCV Ab+ with reflex to positive HCV PCR
- Patient/parent/LAR unable to give informed consent/
- Subject Exclusion: Treatment with CD371-specific/YSNVz/IL-18 CAR T cells (Part B)
- Bridging chemotherapy occurring < 1 week prior to administration of LDC
- o Exception: hydroxyurea can be continued up to 72 hours prior to leukapheresis or 24 hours prior to LDC
- Pregnant or lactating women
- Radiographically-detected or symptomatic CNS disease or CNS 3 disease (i.e., presence of ≥ 5/ul WBC in CSF). Subjects with adequately treated CNS leukemia are eligible.
- Isolated extramedullary disease
- Lack of a suitable donor/source for allogeneic HSCT as determined by the treating physician.
- Patients with prior alloHCT are allowed as long as alloHCT occurred ≥100 days prior to date of treatment with CD371-specific/YSNVz/IL-18 CAR T cells and as long as the patient is without ongoing requirement for systemic graft-versus-host therapy
- Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject
- Impaired cardiac function (LVEF < 50%) as assessed by ECHO or MUGA scan.
- Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction ≤ 6 months prior to enrollment
- History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- Positive serologic test results for HIV.
- Acute or chronic HBV infection as assessed by serologic (HBVsAg) or PCR results, defined as HBVsAg+, HBVcAb+, HBV PCR+.
- Acute or chronic HCV infection as assessed by serologic (HCV ab) or PCR results, defined as HCV Ab+ with reflex to positive HCV PCR
- Active second malignancy that requires systemic treatments, with the exception of malignancy treated with curative intent and without evidence of disease for > 2 years before screening
- Patient/parent/LAR unable to give informed consent
- Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study; conditions that in the Principal Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activities)
Commack, New York, 11725
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Monmouth (Limited protocol activities)
Middletown, New Jersey, 07748
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Cancer Center (All protocol activites)
New York, New York, 10065
Mark Geyer, MD, 646-608-3745
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activites)
Rockville Centre, New York, 11553
Mark Geyer, MD, 646-608-3745
About this study
Official title: Phase I Trial of CLEc12a (CD371) Targeted ArmoRed Immune Effector Cells in Patients With Relapsed/Refractory Acute Myeloid Leukemia (CLEAR-AML)
The purpose of this study is to find out whether CD371-YSNVZ-IL18 CAR T cells are safe, and to look for the highest dose of CD371-YSNVZ-IL18 CAR T cells that cause few or mild side effects in participants.
- Conditions
- Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory
- Being tested
- CD371-specific/YSNVz/I-18 CAR T cells
- Keywords
- Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory, ArmoRed, CLEAR-AML, CLEc12a, CD371, Memorial Sloan Kettering Cancer Center, 23-016
- 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.
CD371-specific/YSNVz/I-18 CAR T cellsBiological
Cohorts will be infused with escalating doses of CD371-specific/YSNVz/IL-18 CAR T cells with lymphodepleting chemotherapy (LDC) to establish the maximum tolerated dose (MTD). There is a third, lower dose level (step-down dose) available for dose de-escalation in the event of severe toxicity at the first planned dose level.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Receives: Biological: CD371-specific/YSNVz/I-18 CAR T cells |
| Dose Level 2 | Experimental | Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Receives: Biological: CD371-specific/YSNVz/I-18 CAR T cells |
| Step-Down Dose | Experimental | Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Receives: Biological: CD371-specific/YSNVz/I-18 CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of CAR T cells
Determine the Maximum Tolerated Dose/MTD of CAR T cells in participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
1 Sep 202317 Dec 2027
- First posted30 Aug 2023
- Study start1 Sep 2023
- Primary completion17 Dec 2027 (estimated)
- Study completion17 Dec 2027 (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 Refractory Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Geyer, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06017258
- Sponsor's protocol ID
- 23-016
- Status last verified
- Oct 2026
- First submitted
- 24 Aug 2023
- Last updated
- 6 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Publications
Geyer MB, DeWolf S, Mi X, Weis K, Shaffer BC, Cadzin B, McAvoy D, Katsamakis Z, Lorenc R, Lewis AM, Gipson B, Cuibus MA, Girotra NN, Wu K, Smith N, Burns ER, Um JS, Yoo S, Masouleh BK, Galera P, Hosszu K, Chaudhari J, Wang X, Lin Q, Curran KJ, Park JH, Scheinberg DA, van den Brink MRM, Abdel-Wahab O, Brentjens RJ, Daniyan AF. CD371-targeted CAR T cells secreting interleukin-18 exhibit robust expansion and clear refractory acute myeloid leukemia. Blood. 2025 Dec 25;146(26):3163-3174. doi: 10.1182/blood.2025029532.
PubMed 40864984