Relapsed/Refractory Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, Chimeric Antigen Receptor T-Cell (CAR-T) therapy, Allogeneic, Transcription Activator-Like Effector Nuclease (TALEN)
Brief summary
Phase I, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of Universal Chimeric Antigen Receptor T-cell (UCART) targeting the Cluster of Differentiation 123 (CD123) in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of Universal Chimeric Antigen Receptor T-cells targeting CD123 (UCART123v1.2) and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).
Interventions
BIOLOGICALUCART123v1.2
Allogeneic engineered T-cells expressing anti-CD123 Chimeric Antigen Receptor Biological/vaccine: CLLS52 A monoclonal antibody that recognizes the CD52 antigen Other Names: Alemtuzumab
Sponsors
Cellectis S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patients with relapsed or primary refractory AML (as defined in World Health Organization \[WHO\] criteria) with ≥5% bone marrow blasts * Patients with CD123+ blast cells (verified by flow cytometry) * Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of ≤1 * Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within screening period * (Dose-escalation) Identified donor and transplant strategy prior to lymphodepletion (LD) * Other criteria may apply Main
Exclusion criteria
* Patients with acute promyelocytic leukemia (APL) or central nervous system (CNS) Leukemia * Previous investigation gene or cell therapy (including CAR) * \> 1 prior allogeneic stem cell transplantations (SCTs) * Prior treatment with rituximab or other anti-cluster of differentiation 20 (anti-CD20) therapy within 3 months * Any known active or uncontrolled infection * Other criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability] | 24 Months | Safety of UCART123v1.2 - Incidence, nature, and severity of AE and SAEs throughout the study |
| Dose escalation and expansion part: Occurrence of DLTs | Up to Day 28 post last UCART123v1.2 infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain total area under curve from zero to infinity (AUC-infinity) | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Rate | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Half-life | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Investigators assessed overall response rate according to the European Leukemia Net (ELN) Response Criteria | At Day 28, Day 56, Day 84, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24 |
| Duration of Response | From the date of the initial response to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24 |
| Progression Free Survival | From the first day of study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24 |
| Overall Survival | From the first day of study treatment to the date of death from any cause, assessed up to Month 24 |
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Clearance | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Volume of Distribution | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Pharmacodynamic Analysis: Pharmacodynamics Monitoring of the incidence of anti-cluster of differentiation 52 (anti-CD52; alemtuzumab) antibodies (ADA) in serum Pre-alemtuzumab administration and through Day 84 | From screening through Day 84 |
| Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood | From screening through Day 84 |
| Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood | From screening through Day 84 |
| Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood | From screening through Day 84 |
| Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood | From screening through Day 84 |
| Pharmacokinetic (PK) Analysis: Standard PK Analysis will be completed to obtain Maximum plasma concentration (Cmax) | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
| Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain time to reach Cmax (Tmax) | alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose |
Countries
United States
Outcome results
None listed