Clinical Study of ARD103 CAR-T Therapy for Patients With R/R AML or MDS

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory; MDS (Myelodysplastic Syndrome)
• Interventions: Biological: ARD103; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT06680752
• Lead Sponsor: ARCE Therapeutics, Inc.

Brief Summary

This is a phase I/2, interventional, open-label, multicenter study to assess the safety and efficacy of ARD103 in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.

Detailed Description

The investigational product (IP) for this study is ARD103, a C-type lectin-like molecule-1 (CLL-1) autologous chimeric antigen receptor T-cells (CAR-T). CLL-1 is highly expressed on both myeloid blasts and leukemia stem cells (LSCs) but is absent on normal hematopoietic stem cells (HSCs), suggesting CLL-1 as an excellent therapeutic target for AML and hence other potential myeloid malignancies.

Study Timeline

• Study First Submitted: 2024-10-29
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-07
• Study First Posted: 2024-11-08
• Study Start: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-09
• Primary Completion: 2028-10
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

• Documented diagnosis of AML with either refractory or relapsed disease or diagnosis of MDS and ≥ 5% BM blasts

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate hematologic status:

  • Absolute lymphocyte count (ALC) > 100/mm3

• Adequate renal, hepatic, cardiac and pulmonary function:

  • ALT and AST < 3.0 × the ULN
  • Creatinine clearance ≥ 45.0 mL/min as estimated by Cockcroft-Gault and independent dialysis
  • Total bilirubin ≤ 2.0 mg/dL

• Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test

• Contraception: males and females of childbearing potential must agree to use an effective method of contraception

• Participant is capable of giving signed informed consent

Exclusion Criteria

• Participants with acute promyelocytic leukemia
• Presence of active and clinically relevant central nervous system (CNS) disorder
• Autoimmune disease requiring immunosuppressive treatment
• Participants with known hepatic bridging cirrhosis
• Currently active infection with hepatitis B or C
• Previous treatment with investigational gene or cell therapy (including CAR therapy)
• Any active acute GvHD or systemic treatment of more than 10 mg prednisone daily (or equivalent)
• Previous chemotherapy including biologic/targeted therapy or immunological agents directed to the pathology within 14 days prior to screening and all along the study duration

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)	ARD103	In Phase 1, three escalating dose levels will be tested using the 3 + 3 design. The MTD and RP2D will be identified. The Phase 2 will be conducted in 2 stages. In Stage I, evaluable participants from Phase 1 treated at RP2D will be enrolled. And the enrollment will continue into Stage II (additional evaluable participants) at the maximum RP2D participants for preliminary overall assessment of efficacy and safety.
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)	Cyclophosphamide	In Phase 1, three escalating dose levels will be tested using the 3 + 3 design. The MTD and RP2D will be identified. The Phase 2 will be conducted in 2 stages. In Stage I, evaluable participants from Phase 1 treated at RP2D will be enrolled. And the enrollment will continue into Stage II (additional evaluable participants) at the maximum RP2D participants for preliminary overall assessment of efficacy and safety.
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)	Fludarabine	In Phase 1, three escalating dose levels will be tested using the 3 + 3 design. The MTD and RP2D will be identified. The Phase 2 will be conducted in 2 stages. In Stage I, evaluable participants from Phase 1 treated at RP2D will be enrolled. And the enrollment will continue into Stage II (additional evaluable participants) at the maximum RP2D participants for preliminary overall assessment of efficacy and safety.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	28 days post ARD103 infusion	The records of AEs and severity following the first infusion of ARD103.
To determine the RP2D of ARD103	28 days post ARD103 infusion	RP2D of ARD103 following a 3+3 dose escalation schema (Phase 1)
To evaluate overall response rate (ORR)	Up to 24 months	The ORR will be evaluated by European Leukemia Net (ELN) criteria

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	First infusion date of ARD103 up to 15 years	OS is defined as the time from ARD103 infusion to the date of death from any cause.
Progression-free survival (PFS)	Up to 24 months	PFS is defined as the time from the infusion of ARD103 infusion to the first recorded response of disease progression, relapse, or death due to any cause, whichever occurs first.
Time to best response	First infusion date of ARD103 up to 24 months	Time to best response is defined as the time from the infusion of ARD103 to the BOR.

Trial Locations

Locations (1)

Novant Health Cancer Institute; 🇺🇸 Winston Salem, North Carolina, United States