A Phase 1/2, Open-label, Multicenter Trial to Assess the Safety and Efficacy of ARD103 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Overview
- Phase
- Phase 1
- Intervention
- ARD103
- Conditions
- Acute Myeloid Leukemia, in Relapse
- Sponsor
- ARCE Therapeutics, Inc.
- Enrollment
- 49
- Locations
- 2
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)
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.
Intervention: ARD103
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)
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.
Intervention: Cyclophosphamide
phase 1 (Dose Escalation) and phase 2 (Dose Expansion)
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.
Intervention: Fludarabine
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 28 days post ARD103 infusion
The records of AEs and severity following the first infusion of ARD103.
To determine the RP2D of ARD103
Time Frame: 28 days post ARD103 infusion
RP2D of ARD103 following a 3+3 dose escalation schema (Phase 1)
To evaluate overall response rate (ORR)
Time Frame: Up to 24 months
The ORR will be evaluated by European Leukemia Net (ELN) criteria
Secondary Outcomes
- Overall Survival (OS)(First infusion date of ARD103 up to 15 years)
- Progression-free survival (PFS)(Up to 24 months)
- Time to best response(First infusion date of ARD103 up to 24 months)