Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory, MDS (Myelodysplastic Syndrome)
Conditions
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.
Interventions
BIOLOGICALARD103
ARD103 autologous CAR-T cell therapy targeting CLL-1, single iv. infusion
DRUGCyclophosphamide
iv administration for lymphodepletion
DRUGFludarabine
iv administration for lymphodepletion
Sponsors
ARCE Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactARCE Therapeutics, Inc
Outcome results
None listed