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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase I Study of ADCLEC.syn1 CAR T Cells in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05748197
• Other study ID #: 23-002
• Status: Recruiting
• Phase: Phase 1
• Start date: April 18, 2024
• Est. completion date: April 18, 2028

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Jae Park, MD
• Phone: 646-608-2091
• Email: parkj6[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 18, 2028
• Est. primary completion date: April 18, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years of age at the time of signing informed consent.

2. 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.

3. ECOG performance status 0 or 1.

4. 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.

5. Adequate organ function defined as:

1. Serum creatinine <2.0 mg/100 mL.

2. Total bilirubin <2.0 mg/100 mL, unless benign congenital hyperbilirubinemia or due to leukemia organ involvement

3. AST and/or ALT =5 × ULN, unless considered due to leukemic organ involvement.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia.

2. 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.

3. Oxygen saturation <90% on room air.

4. 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.

5. Treatment with clofarabine or cladribine within 3 months prior to leukapheresis

6. The following medications are excluded:

1. 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.

2. Chemotherapy: Should be stopped one week prior to leukapheresis or starting conditioning chemotherapy. Hydroxyurea for cytoreduction can be administered up to 72 hours before leukapheresis or CAR T cell infusion.

7. 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%.

8. Uncontrolled clinically significant infections such as ongoing fever for 48 hours, persistent bacteremia or requiring new supplemental oxygen.

9. Previous treatment with CAR therapy

10. Positive serologic test results for HIV.

11. Acute or chronic HBV infection as assessed by serologic (HBVsAg) or PCR results, defined as HBVsAg+, HBVcAb+, HBV PCR+. 12. Acute or chronic HCV infection as assessed by serologic (HCV ab) or PCR results, defined as HCV Ab+ with reflex to positive HCV PCR.

13. 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.

14. Live vaccine within 4 weeks prior to leukapheresis 15. Pregnant or lactating/breastfeeding women 16. Any prior or ongoing condition/issue that in the opinion of the investigator would make the patient ineligible for study

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• ADCLEC.syn1 CAR T cells
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.

Drug:
• Conditioning chemotherapy
Fludarabine 30 mg/m2 daily for 3 days and cyclophosphamide 500 mg/m2 daily for 3 days.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Takeda

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Memorial Sloan Kettering Cancer Center