A Study of ADCLEC.syn1 in People With Acute Myeloid Leukemia

NCT05748197 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 23-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of ADCLEC.syn1 CAR T cells in people with relapsed or refractory AML. The researchers will try to find the highest dose of ADCLEC.syn1 CAR T cells that causes few or mild side effects in participants. Once the researchers find this dose, it will test it in a new group of participants to see if it is effective in treating their relapsed/refractory AML.

Conditions

Acute Myeloid Leukemia

Keywords

Relapsed; Refractory; ADCLEC.syn1 CAR T cells; Cyclophosphamide; Fludarabine; 23-002

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  Dose escalation of ADCLEC.syn1 CAR T cells will follow Bayesian optimal interval (BOIN) design to inform dose-escalation decisions and potential maximum tolerated dose (MTD) estimation. Patients will be enrolled in cohorts of 3.

  2 years

Study Arms (1)

ADCLEC.syn1 CAR T cells

EXPERIMENTAL

The dose escalation cohort size of 3 patients in each cohort will be infused with escalating doses of ADCLEC.syn1 CAR T cells to inform the RP2D. There are 4 planned flat-dose levels: 25 × 10\^6, 75 × 10\^6 , 225 × 10\^6 , and 450 × 10\^6 CAR T cells and 1 de-escalation dose: 10 × 10\^6 CAR T cells. After dose escalation, one or two dose levels will be selected for dose expansion cohort(s).Two to 7 days following completion of the conditioning chemotherapy, the frozen CAR T cells will be thawed and administered. Conditioning chemotherapy may occur either outpatient or inpatient, and T cell infusions will occur as inpatient. Up to approximately 12 additional patients each if two doses are selected or approximately 16 additional patients, if one dose is selected, will be treated in the dose expansion phase to determine RP2D.

Biological: ADCLEC.syn1 CAR T cells; Drug: Conditioning chemotherapy

Interventions

Conditioning chemotherapy DRUG

Fludarabine 30 mg/m2 daily for 3 days and cyclophosphamide 500 mg/m2 daily for 3 days.

ADCLEC.syn1 CAR T cells

ADCLEC.syn1 CAR T cells BIOLOGICAL

There are 4 planned flat-dose levels: 25 × 10\^6, 75 × 10\^6 , 225 × 10\^6 , and 450 × 10\^6 CAR T cells and 1 de-escalation dose: 10 × 10\^6 CAR T cells.

ADCLEC.syn1 CAR T cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age at the time of signing informed consent.
• Patients must have R/R AML. The following disease status will be eligible for the study:
• a. Refractory AML is defined as failure to achieve a CR, CRh or CRi after one of the following regimens: i. At least one course of standard intensive induction chemotherapy (e.g., 7+3, MEC, HiDAC, etc.) or hypomethylating agent (HMA) or low dose cytarabine-based combination regimen including but not limited to venetoclax (e.g. venetoclax in combination with azacytidine, decitabine or cytarabine) ii. Four cycles of HMA monotherapy b. Relapsed AML is defined the appearance of ≥5% blasts in the bone marrow or peripheral blood at any time after achieving a CR, CRh, or CRi.
• ECOG performance status 0 or 1.
• Subjects must have a suitable stem cell donor identified who may donate cells in the event that the subject needs to undergo an allogeneic HSCT for rescue from prolonged marrow aplasia.
• Donor may be from related or unrelated matched source, haplo or cord, and must be found to be suitable according to the institution's standard criteria.
• Adequate organ function defined as:
• Serum creatinine \<2.0 mg/100 mL.
• Total bilirubin \<2.0 mg/100 mL, unless benign congenital hyperbilirubinemia or due to leukemia organ involvement
• AST and/or ALT ≤5 × ULN, unless considered due to leukemic organ involvement.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia.
• Radiologically-detected or symptomatic CNS disease or CNS 3 disease (i.e., presence of ≥5/µL WBCs in CSF). Subjects with adequately treated CNS leukemia are eligible.
• Oxygen saturation \<90% on room air.
• Patients with prior allogeneic HSCT are allowed as long as HSCT occurred \> 3 months of signing ICF and without ongoing requirement for systemic graft-versus-host therapy.
• Treatment with clofarabine or cladribine within 3 months prior to leukapheresis
• The following medications are excluded:
• Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion.
• Chemotherapy: Bridging chemotherapy including venetoclax must be discontinued at least 1 week prior to administration of conditioning chemotherapy, but FDA-approved oral targeted therapies such as IDH1/2, FLT3, and menin inhibitiors as well as hydroxyurea can be continued until at least 24 hours prior to the start of conditioning chemotherapy
• Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months prior to first study medication; or the presence of unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher; or cardiac ejection fraction \<40%.
• Uncontrolled clinically significant infections such as ongoing fever for 48 hours, persistent bacteremia or requiring new supplemental oxygen.
• 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.
• Live vaccine within 4 weeks prior to leukapheresis

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Takeda: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Publications (1)

• Haubner S, Mansilla-Soto J, Nataraj S, Kogel F, Chang Q, de Stanchina E, Lopez M, Ng MR, Fraser K, Subklewe M, Park JH, Wang X, Riviere I, Sadelain M. Cooperative CAR targeting to selectively eliminate AML and minimize escape. Cancer Cell. 2023 Nov 13;41(11):1871-1891.e6. doi: 10.1016/j.ccell.2023.09.010. Epub 2023 Oct 5.

  PMID: 37802054 BACKGROUND

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jae Park, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jae Park, MD

CONTACT

646-608-2091; parkj6@mskcc.org

Mark Geyer, MD

CONTACT

646-608-3745

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I, open-label, dose-escalation/dose expansion trial.

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: February 28, 2023
• Study Start: April 18, 2024
• Primary Completion (Estimated): April 18, 2028
• Study Completion (Estimated): April 18, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)